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Zhang Y, Yue NN, Chen LY, Tian CM, Yao J, Wang LS, Liang YJ, Wei DR, Ma HL, Li DF. Exosomal biomarkers: A novel frontier in the diagnosis of gastrointestinal cancers. World J Gastrointest Oncol 2025; 17:103591. [PMID: 40235899 PMCID: PMC11995328 DOI: 10.4251/wjgo.v17.i4.103591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/24/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
Gastrointestinal (GI) cancers, which predominantly manifest in the stomach, colorectum, liver, esophagus, and pancreas, accounting for approximately 35% of global cancer-related mortality. The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers. This non-invasive technique not only facilitates prompt therapeutic intervention, but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence. The wealth of circulating exosomes present in body fluids is often enriched with proteins, lipids, microRNAs, and other RNAs derived from tumor cells. These specific cargo components are reflective of processes involved in GI tumorigenesis, tumor progression, and response to treatment. As such, they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer. In this review, we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles. We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application. Furthermore, we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.
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Affiliation(s)
- Yuan Zhang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
- Department of Medical Administration, Huizhou Institute for Occupational Health, Huizhou 516000, Guangdong Province, China
| | - Ning-Ning Yue
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), Shenzhen 518000, Guangdong Province, China
| | - Li-Yu Chen
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People’s Hospital (Jinan University of Second Clinical Medical Sciences), Shenzhen 518000, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen 518000, Guangdong Province, China
| | - Dao-Ru Wei
- Department of Rehabilitation, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Hua-Lin Ma
- Department of Nephrology, The Second Clinical Medical College, Jinan University, Shenzhen 518020, Guangdong Province, China
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
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Delshad M, Sanaei MJ, Mohammadi MH, Sadeghi A, Bashash D. Exosomal Biomarkers: A Comprehensive Overview of Diagnostic and Prognostic Applications in Malignant and Non-Malignant Disorders. Biomolecules 2025; 15:587. [PMID: 40305328 PMCID: PMC12024574 DOI: 10.3390/biom15040587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 04/07/2025] [Accepted: 04/09/2025] [Indexed: 05/02/2025] Open
Abstract
Exosomes are small extracellular vesicles, ranging from 30 to 150 nm, that are essential in cell biology, mediating intercellular communication and serving as biomarkers due to their origin from cells. Exosomes as biomarkers for diagnosing various illnesses have gained significant investigation due to the high cost and invasive nature of current diagnostic procedures. Exosomes have a clear advantage in the diagnosis of diseases because they include certain signals that are indicative of the genetic and proteomic profile of the ailment. This feature gives them the potential to be useful liquid biopsies for real-time, noninvasive monitoring, enabling early cancer identification for the creation of individualized treatment plans. According to our analysis, the trend toward utilizing exosomes as diagnostic and prognostic tools has raised since 2012. In this regard, the proportion of malignant indications is higher compared with non-malignant ones. To be precise, exosomes have been used the most in gastrointestinal, thoracic, and urogenital cancers, along with cardiovascular, diabetic, breathing, infectious, and brain disorders. To the best of our knowledge, this is the first research to examine all registered clinical trials that look at exosomes as a diagnostic and prognostic biomarker.
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Affiliation(s)
- Mahda Delshad
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
- Department of Laboratory Sciences, School of Allied Medical Sciences, Zanjan University of Medical Sciences, Zanjan 1411718541, Iran
| | - Mohammad-Javad Sanaei
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
| | - Mohammad Hossein Mohammadi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran; (M.D.); (M.-J.S.); (M.H.M.)
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Noyan S, Dedeoğlu BG. Upregulation of miR-99b-5p Modulates ESR1 Expression as an Adaptive Mechanism to Circumvent Drug Response via Facilitating ER/HER2 Crosstalk. Balkan Med J 2025; 42:150-156. [PMID: 40033677 PMCID: PMC11881538 DOI: 10.4274/balkanmedj.galenos.2025.2024-12-47] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 02/17/2025] [Indexed: 03/05/2025] Open
Abstract
Background Endocrine resistance remains a significant therapeutic challenge in estrogen receptor-positive (ER+) breast cancer, the most common subtype, contributing to increased morbidity and mortality. The interaction between ER and HER family receptors, particularly HER2 and epidermal growth factor receptor (EGFR), drives resistance to standard therapies such as tamoxifen and trastuzumab by activating key signaling pathways, including PI3K/AKT and RAS/MAPK. Dysregulated miRNAs, which are non-coding gene expression regulators, have been linked to therapy response. Aims To investigate the role of miR-99b-5p in ER-HER2/EGFR crosstalk in BT-474 cells. Study Design Experimental study. Methods The expression profile and prognostic significance of miR- 99b-5p in breast cancer were analyzed using The Cancer Genome Atlas (TCGA) database. BT-474 cells were transfected with miR-99b-5p mimics and inhibitors, followed by treatment with tamoxifen and trastuzumab to assess their impact on cell proliferation and ER-HER2/EGFR crosstalk. Western blotting was performed to quantify EGFR, HER2, and ESR1 protein levels. Real-time proliferation analysis evaluated changes in cell growth following miRNA transfection and drug treatment. Results The study revealed that miR-99b-5p is significantly overexpressed in tumors compared to normal tissues and is associated with poor patient survival and enhanced ER signaling. Transfection with miR-99b-5p mimics increased ESR1 expression and cell proliferation, even in the presence of tamoxifen or trastuzumab, indicating that miR-99b-5p contributes to therapy resistance through receptor crosstalk. Conversely, miR-99b-5p inhibition significantly restored drug sensitivity, reducing proliferation and enhancing the effectiveness of tamoxifen and trastuzumab. Conclusion These findings establish miR-99b-5p as a key regulator of endocrine and HER2-targeted therapy resistance. Targeting miR-99b-5p could represent a potential therapeutic strategy to improve treatment outcomes in ER+/HER2+ breast cancer. Further research is needed to clarify the underlying molecular mechanisms and validate the therapeutic potential of miR-99b-5p inhibition in clinical applications.
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Affiliation(s)
- Senem Noyan
- Biotechnology Institute Ankara University, Ankara, Türkiye
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Gralewska P, Biegała Ł, Gajek A, Szymczak-Pajor I, Marczak A, Śliwińska A, Rogalska A. Olaparib Combined with DDR Inhibitors Effectively Prevents EMT and Affects miRNA Regulation in TP53-Mutated Epithelial Ovarian Cancer Cell Lines. Int J Mol Sci 2025; 26:693. [PMID: 39859407 PMCID: PMC11766100 DOI: 10.3390/ijms26020693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial-mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and migratory capabilities, often driven by changing miRNA expression involved in the regulation of pathological processes like drug resistance. Targeted therapies like PARP inhibitors (PARPi) have improved outcomes, particularly in BRCA-mutated and DNA repair-deficient tumors; however, resistance and limited efficacy in advanced stages remain challenges. Recent studies highlight the potential synergy of PARPi with DNA damage response (DDR) inhibitors, such as ATR and CHK1 inhibitors, which disrupt cancer cell survival pathways under stress. This study investigated the combined effects of olaparib with ATR and CHK1 inhibitors (ATRi and CHK1i) on migration, invasion, and EMT-related protein expression and miRNA expression in ovarian cancer cell lines OV-90 and SKOV-3. The results demonstrated enhanced cytotoxicity, inhibition of migration and invasion, and modulation of miRNAs linked to metastasis. These findings suggest that combination therapies targeting DNA repair and cell cycle pathways may offer a novel, more effective approach to managing advanced EOC and reducing metastatic spread.
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Affiliation(s)
- Patrycja Gralewska
- Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland; (P.G.); (Ł.B.); (A.G.); (A.M.)
| | - Łukasz Biegała
- Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland; (P.G.); (Ł.B.); (A.G.); (A.M.)
| | - Arkadiusz Gajek
- Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland; (P.G.); (Ł.B.); (A.G.); (A.M.)
| | - Izabela Szymczak-Pajor
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Street, 92-213 Lodz, Poland; (I.S.-P.); (A.Ś.)
| | - Agnieszka Marczak
- Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland; (P.G.); (Ł.B.); (A.G.); (A.M.)
| | - Agnieszka Śliwińska
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 251 Pomorska Street, 92-213 Lodz, Poland; (I.S.-P.); (A.Ś.)
| | - Aneta Rogalska
- Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland; (P.G.); (Ł.B.); (A.G.); (A.M.)
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Wang Y, Xiong J, Ouyang K, Ling M, Luo J, Sun J, Xi Q, Chen T, Zhang Y. Extracellular vesicles: From large-scale production and engineering to clinical applications. J Tissue Eng 2025; 16:20417314251319474. [PMID: 40322740 PMCID: PMC12048759 DOI: 10.1177/20417314251319474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Indexed: 05/08/2025] Open
Abstract
Extracellular vesicles (EVs) have emerged as a promising strategy for treating a wide spectrum of pathologies, as they can deliver their cargo to recipient cells and regulate the signaling pathway of these cells to modulate their fate. Despite the great potential of EVs in clinical applications, their low yield and the challenges of cargo loading remain significant obstacles, hindering their transition from experimental research to clinical practice. Therefore, promoting EV release and enhancing EV cargo-loading are promising fields with substantial research potential and broad application prospects. In this review, we summarize the clinical applications of EVs, the methods and technologies for their large-scale production, engineering, and modification, as well as the challenges that must be addressed during their development. We also discuss the future perspectives of this exciting field of research to facilitate its transformation from bench to clinical reality.
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Affiliation(s)
- Yuxuan Wang
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
| | - Jiali Xiong
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
- College of Medicine, Jiaxing University, Jiaxing, Zhejiang, China
| | - Kun Ouyang
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
| | - Mingwang Ling
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
| | - Junyi Luo
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
| | - Jiajie Sun
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
| | - Qianyun Xi
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
| | - Ting Chen
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
| | - Yongliang Zhang
- College of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural University, Guangzhou, Guangdong, China
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Huang C, Li J, Xie Z, Hu X, Huang Y. Relationship between exosomes and cancer: formation, diagnosis, and treatment. Int J Biol Sci 2025; 21:40-62. [PMID: 39744442 PMCID: PMC11667803 DOI: 10.7150/ijbs.95763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 11/02/2024] [Indexed: 01/11/2025] Open
Abstract
Exosomes are a member of extracellular vesicles. However, their biological characteristics differ from those of other vesicles, and recently, their powerful functions as information molecules, biomarkers, and carriers have been demonstrated. Malignancies are the leading cause of high morbidity and mortality worldwide. The cure rate of malignancies can be improved by improving early screening rates and therapy. Moreover, a close correlation between exosomes and malignancies has been observed. An in-depth study of exosomes can provide new methods for diagnosing and treating tumors. Therefore, this study aimed to review, sort, and summarize such achievements, and present ideas and opinions on the application of exosomes in tumor treatment.
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Affiliation(s)
- Chen Huang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jiajin Li
- Sichuan university, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Zichuan Xie
- Sichuan university, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xiangjun Hu
- Sichuan university, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yan Huang
- Health Management Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China
- State Key Laboratory of Respiratory Health and Multimorbidity, China
- Research Laboratory for Prediction and Evaluation of Chronic Diseases in the Elderly, National Clinical Research Center for Geriatric Diseases, China
- General Practice Research Institute, West China Hospital, Sichuan University, Chengdu, China
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Vékony B, Nyirő G, Herold Z, Fekete J, Ceccato F, Gruber S, Kürzinger L, Parasiliti-Caprino M, Bioletto F, Szücs N, Doros A, Szeredás BK, Syed Mohammed Nazri SK, Fell V, Bassiony M, Dank M, Azizan EA, Bancos I, Beuschlein F, Igaz P. Circulating miRNAs and Machine Learning for Lateralizing Primary Aldosteronism. Hypertension 2024; 81:2479-2488. [PMID: 39417220 PMCID: PMC11578053 DOI: 10.1161/hypertensionaha.124.23418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 09/19/2024] [Indexed: 10/19/2024]
Abstract
BACKGROUND Distinguishing between unilateral and bilateral primary aldosteronism, a major cause of secondary hypertension, is crucial due to different treatment approaches. While adrenal venous sampling is the gold standard, its invasiveness, limited availability, and often difficult interpretation pose challenges. This study explores the utility of circulating microRNAs (miRNAs) and machine learning in distinguishing between unilateral and bilateral forms of primary aldosteronism. METHODS MiRNA profiling was conducted on plasma samples from 18 patients with primary aldosteronism taken during adrenal venous sampling on an Illumina MiSeq platform. Bioinformatics and machine learning identified 9 miRNAs for validation by reverse transcription real-time quantitative polymerase chain reaction. Validation was performed on a cohort consisting of 108 patients with known subdifferentiation. A 30-patient subset of the validation cohort involved both adrenal venous sampling and peripheral, the rest only peripheral samples. A neural network model was used for feature selection and comparison between adrenal venous sampling and peripheral samples, while a deep-learning model was used for classification. RESULTS Our model identified 10 miRNA combinations achieving >85% accuracy in distinguishing unilateral primary aldosteronism and bilateral adrenal hyperplasia on a 30-sample subset, while also confirming the suitability of peripheral samples for analysis. The best model, involving 6 miRNAs, achieved an area under curve of 87.1%. Deep learning resulted in 100% accuracy on the subset and 90.9% sensitivity and 81.8% specificity on all 108 samples, with an area under curve of 86.7%. CONCLUSIONS Machine learning analysis of circulating miRNAs offers a minimally invasive alternative for primary aldosteronism lateralization. Early identification of bilateral adrenal hyperplasia could expedite treatment initiation without the need for further localization, benefiting both patients and health care providers.
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Affiliation(s)
- Bálint Vékony
- Department of Endocrinology (B.V., G.N., N.S., B.K.S., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Oncology (B.V., G.N., Z.H., N.S., B.K.S., M.D., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Gábor Nyirő
- Department of Endocrinology (B.V., G.N., N.S., B.K.S., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Oncology (B.V., G.N., Z.H., N.S., B.K.S., M.D., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Department of Laboratory Medicine (G.N.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Zoltan Herold
- Department of Internal Medicine and Oncology (B.V., G.N., Z.H., N.S., B.K.S., M.D., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - János Fekete
- Department of Bioinformatics (J.F.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Filippo Ceccato
- Endocrinology Unit, Department of Medicine, University of Padova, Italy (F.C.)
- Endocrinology Unit, University-Hospital of Padova, Italy (F.C.)
| | - Sven Gruber
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital and University of Zurich, Switzerland (S.G., F. Beuschlein)
| | - Lydia Kürzinger
- Department of Internal Medicine I, Division of Endocrinology and Diabetes, University of Würzburg, Germany (L.K.)
| | - Mirko Parasiliti-Caprino
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Italy (M.P.-C., F. Bioletto)
| | - Fabio Bioletto
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Italy (M.P.-C., F. Bioletto)
| | - Nikolette Szücs
- Department of Endocrinology (B.V., G.N., N.S., B.K.S., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Oncology (B.V., G.N., Z.H., N.S., B.K.S., M.D., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Attila Doros
- Department of Imaging and Medical Instrumentation, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary (A.D.)
| | - Bálint Kende Szeredás
- Department of Endocrinology (B.V., G.N., N.S., B.K.S., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Oncology (B.V., G.N., Z.H., N.S., B.K.S., M.D., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | | | - Vanessa Fell
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine (V.F., M.B., I.B.), Mayo Clinic, Rochester, MN
| | - Mohamed Bassiony
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine (V.F., M.B., I.B.), Mayo Clinic, Rochester, MN
| | - Magdolna Dank
- Department of Internal Medicine and Oncology (B.V., G.N., Z.H., N.S., B.K.S., M.D., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Elena Aisha Azizan
- Department of Medicine, Faculty of Medicine, The National University of Malaysia, Kuala Lumpur (S.K.S.M.N., E.A.A.)
| | - Irina Bancos
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine (V.F., M.B., I.B.), Mayo Clinic, Rochester, MN
- Department of Laboratory Medicine and Pathology (I.B.), Mayo Clinic, Rochester, MN
| | - Felix Beuschlein
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital and University of Zurich, Switzerland (S.G., F. Beuschlein)
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität, Munich, Germany (F. Beuschlein)
- The LOOP Zurich - Medical Research Center, Zurich, Switzerland (F. Beuschlein)
| | - Peter Igaz
- Department of Endocrinology (B.V., G.N., N.S., B.K.S., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Department of Internal Medicine and Oncology (B.V., G.N., Z.H., N.S., B.K.S., M.D., P.I.), Faculty of Medicine, Semmelweis University, Budapest, Hungary
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XU LICHEN, ZHANG PAN, ZHANG GUIQI, SHEN ZHAOLIANG, BAI XIZHUANG. MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma. Oncol Res 2024; 32:1777-1789. [PMID: 39449798 PMCID: PMC11497191 DOI: 10.32604/or.2024.047704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 04/07/2024] [Indexed: 10/26/2024] Open
Abstract
Background Osteosarcoma (OS), recognized as the predominant malignant tumor originating from bones, necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance treatment methodologies. The role of fat mass and obesity-associated (FTO) in OS, particularly its correlation with malignant traits, and the fundamental mechanism, remains to be elucidated. Materials and Methods 1. The FTO expression and survival rate in tumors were analyzed. 2. FTO in OS cell lines was quantified utilizing western blot and PCR. 3. FTO was upregulated and downregulated separately in MG63. 4. The impact of FTO on the proliferation and migration of OS cells was evaluated using CCK-8, colony formation, wound healing, and Transwell assays. 5. The expression of miR-150-5p in OS cells-derived exosomes was identified. 6. The binding of miR-150-5p to FTO was predicted by TargetScan and confirmed by luciferase reporter assay. 7. The impact of exosome miR-150-5p on the proliferation and migration of OS cells was investigated. Results The expression of FTO was higher in OS tissues compared to normal tissues correlating with a worse survival rate. Furthermore, the downregulation of FTO significantly impeded the growth and metastasis of OS cells. Additionally, miR-150-5p, which was downregulated in both OS cells and their derived exosomes, was found to bind to the 3'-UTR of FTO through dual luciferase experiments. Exosomal miR-150-5p was found to decrease the expression of FTO and inhibit cell viability. Conclusions We identified elevated levels of FTO in OS, which may be attributed to insufficient miR-150-5p levels in both the cells and exosomes. It suggests that the dysregulation of miR-150-5p and its interaction with FTO could potentially promote the development of OS.
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Affiliation(s)
- LICHEN XU
- Dalian Medical University, Dalian, 116044, China
- Department of Spinal Surgery, Dalian Municipal Central Hospital, Dalian, 116033, China
| | - PAN ZHANG
- Department of Orthopaedics, The People’s Hospital of China Medical University, People’s Hospital of Liaoning Province, Shenyang, 110016, China
| | - GUIQI ZHANG
- Department of Spinal Surgery, Dalian Municipal Central Hospital, Dalian, 116033, China
| | - ZHAOLIANG SHEN
- Department of Orthopedic, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China
| | - XIZHUANG BAI
- Dalian Medical University, Dalian, 116044, China
- Department of Orthopaedics, The People’s Hospital of China Medical University, People’s Hospital of Liaoning Province, Shenyang, 110016, China
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Ždralević M, Radović A, Raonić J, Popovic N, Klisic A, Vučković L. Advances in microRNAs as Emerging Biomarkers for Colorectal Cancer Early Detection and Diagnosis. Int J Mol Sci 2024; 25:11060. [PMID: 39456841 PMCID: PMC11507567 DOI: 10.3390/ijms252011060] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 09/21/2024] [Accepted: 09/27/2024] [Indexed: 10/26/2024] Open
Abstract
Colorectal cancer (CRC) remains the second most common cause of cancer-related mortality worldwide, necessitating advancements in early detection and innovative treatment strategies. MicroRNAs (miRNAs), small non-coding RNAs involved in gene regulation, have emerged as crucial players in the pathogenesis of CRC. This review synthesizes the latest findings on miRNA deregulated in precancerous lesions and in CRC. By examining the deregulation patterns of miRNAs across different stages of CRC development, this review highlights their potential as diagnostic tools. We specifically analyse the roles and diagnostic relevance of four miRNAs-miR-15b, miR-21, miR-31, and miR-146a-that consistently exhibit altered expression in CRC. The current knowledge of their role in key oncogenic pathways, drug resistance, and clinical relevance is discussed. Despite challenges posed by the heterogeneity of the research findings on miRNA deregulation and their role in CRC, integrating miRNA diagnostics into current screening methods holds promise for enhancing personalized medicine approaches. This review emphasizes the transformative potential of miRNAs in CRC diagnosis, paving the way for improved patient outcomes and novel therapeutic paradigms.
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Affiliation(s)
- Maša Ždralević
- Institute for Advanced Studies, University of Montenegro, Cetinjska 2, 81000 Podgorica, Montenegro
| | - Andrijana Radović
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
| | - Janja Raonić
- Center for Pathology, Clinical Center of Montenegro, Ljubljanska bb, 81000 Podgorica, Montenegro;
| | - Natasa Popovic
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
| | - Aleksandra Klisic
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
- Center for Laboratory Diagnostics, Primary Health Care Center, 81000 Podgorica, Montenegro
| | - Ljiljana Vučković
- Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro (N.P.); (A.K.); (L.V.)
- Center for Pathology, Clinical Center of Montenegro, Ljubljanska bb, 81000 Podgorica, Montenegro;
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Almutairy B, Alzahrani MS, Waggas DS, Alsaab HO. Particular exosomal micro-RNAs and gastrointestinal (GI) cancer cells' roles: Current theories. Exp Cell Res 2024; 442:114278. [PMID: 39383930 DOI: 10.1016/j.yexcr.2024.114278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/24/2024] [Accepted: 10/06/2024] [Indexed: 10/11/2024]
Abstract
A diverse range of gastrointestinal tract disorders are called gastrointestinal (GI) malignancies. The transformation of normal cells into precursor cells, precursor cells into premalignant cells, and premalignant cells into cancerous cells is facilitated by the interaction of many modifiable and non-modifiable risk factors. Developing relevant therapy alternatives based on a better knowledge of the illness's aetiology is essential to enhance patient outcomes. The exosome is crucial in regulating intercellular interaction because it may send molecular signals to nearby or distant cells. Exosomes produced from cancer can introduce a variety of chemicals and vast concentrations of microRNA (miRNA) into the tumour microenvironment. These miRNAs significantly impact immunological evasion, metastasis, apoptosis resistance, and cell growth. Exosomal miRNAs, or exosomal miRNAs, are essential for controlling cancer resistance to apoptosis, according to mounting data. Exosomal miRNAs function as an interaction hub between cancerous cells and the milieu around them, regulating gene expression and various signalling pathways. Our research examines the regulatory function of exosomal miRNAs in mediating interactions between cancer cells and the stromal and immunological cells that make up the surrounding milieu.
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Affiliation(s)
- Bandar Almutairy
- Department of Pharmacology, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia.
| | - Mohammad S Alzahrani
- Department of Clinical Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
| | - Dania S Waggas
- Pathological Sciences Department, Fakeeh College for Medical Sciences, Jeddah University, Saudi Arabia.
| | - Hashem O Alsaab
- Department of Pharmaceutics and Pharmaceutical Technology, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
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11
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Zhang C, Zhang L, Huang Q, Jiang S, Peng T, Wang S, Xu X. Diagnostic and screening potential of plasma exosome miR‑99b‑5p and its combination with other miRNAs for colorectal cancer. Oncol Lett 2024; 28:461. [PMID: 39119230 PMCID: PMC11307556 DOI: 10.3892/ol.2024.14594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 02/15/2024] [Indexed: 08/10/2024] Open
Abstract
Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.
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Affiliation(s)
- Chang Zhang
- Center of Clinical Aerospace Medicine, School of Aerospace Medicine, Key Laboratory of Aerospace Medicine of Ministry of Education, Air Force Medical University, Xi'an, Shanxi 710032, P.R. China
- Department of Aviation Medicine, The First Affiliated Hospital, Air Force Medical University, Xi'an, Shanxi 710032, P.R. China
| | - Limei Zhang
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
| | - Qiyuan Huang
- Nursing School, Guangzhou Medical University, Guangzhou, Guangdong 510030, P.R. China
| | - Siyuan Jiang
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
| | - Tao Peng
- Sino-French Hoffmann Institute, Guangzhou Hoffman Institute of Immunology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
| | - Shu Wang
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Republic of Singapore
| | - Xuehu Xu
- Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China
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12
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AlZaabi A, Shalaby A. A Systematic Review of Diagnostic Performance of Circulating MicroRNAs in Colorectal Cancer Detection with a Focus on Early-Onset Colorectal Cancer. Int J Mol Sci 2024; 25:9565. [PMID: 39273512 PMCID: PMC11394782 DOI: 10.3390/ijms25179565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 09/15/2024] Open
Abstract
The rising incidence and mortality of early-onset colorectal cancer (EOCRC) emphasize the urgent need for effective non-invasive screening. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for cancer detection. This systematic review aims to evaluate the diagnostic performance of circulating miRNAs in detecting colorectal cancer (CRC). A literature search was conducted in PubMed and Scopus. Studies that report sensitivity, specificity, or area under the curve (AUC) for CRC detection by miRNA were included. The miRNA miR-21 was the most frequently studied biomarker, with a varying range of AUC from 0.55 to 0.973 attributed to differences in study populations and methodologies. The miRNAs miR-210 and miR-1246 showed potential diagnostic capacity with miR-1246 achieving an AUC of 0.924, 100% sensitivity, and 80% specificity. The miRNA panels offer improved diagnostic performance compared to individual miRNA. The best performing panel for CRC patients below 50 is miR-211 + miR-25 + TGF-β1 with AUC 0.99 and 100 specificity and 97 sensitivity. Circulating miRNAs hold significant promise as non-invasive biomarkers for CRC screening. However, the variability in diagnostic performance highlights the need for a standardized method and robust validation studies. Future research should focus on large-scale, ethnically diverse cohorts to establish clinically relevant miRNA biomarkers for CRC, particularly in younger populations.
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Affiliation(s)
- Adhari AlZaabi
- Department of Human and Clinical Anatomy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Asem Shalaby
- Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman;
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Xu J, Pan L, Wu D, Yao L, Jiang W, Min J, Xu S, Deng Z. Comparison of the diagnostic value of various microRNAs in blood for colorectal cancer: a systematic review and network meta-analysis. BMC Cancer 2024; 24:770. [PMID: 38926893 PMCID: PMC11209970 DOI: 10.1186/s12885-024-12528-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Despite the existence of numerous studies investigating the diagnostic potential of blood microRNAs for colorectal cancer, the microRNAs under consideration vary widely, and comparative analysis of their diagnostic value is lacking. Consequently, this systematic review aims to identify the most effective microRNA blood tumor markers to enhance clinical decision-making in colorectal cancer screening. METHOD A comprehensive search of databases, including PubMed, Embase, Web of Science, Scopus, and Cochrane, was conducted to identify case‒control or cohort studies that examined the diagnostic value of peripheral blood microRNAs in colorectal cancer. Studies were included if they provided sensitivity and specificity data, were published in English and were available between January 1, 2000, and February 10, 2023. The Critical Appraisal Skills Programme (CASP) checklist was employed for quality assessment. A Bayesian network meta-analysis was performed to estimate combined risk ratios (RRs) and 95% confidence intervals (CIs), with results presented via rankograms. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202,380,092. RESULTS From an initial pool of 2254 records, 79 met the inclusion criteria, encompassing a total of 90 microRNAs. The seven most frequently studied microRNAs (43 records) were selected for inclusion, all of which demonstrated moderate to high quality. miR-23, miR-92, and miR-21 exhibited the highest sensitivity and accuracy, outperforming traditional tumor markers CA19-9 and CEA in terms of RR values and 95% CI for both sensitivity and accuracy. With the exception of miR-17, no significant difference was observed between each microRNA and CA19-9 and CEA in terms of specificity. CONCLUSIONS Among the most extensively researched blood microRNAs, miR-23, miR-92, and miR-21 demonstrated superior diagnostic value for colorectal cancer due to their exceptional sensitivity and accuracy. This systematic review and network meta-analysis may serve as a valuable reference for the clinical selection of microRNAs as tumor biomarkers.
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Affiliation(s)
- Jianhao Xu
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
- Immunopathology Innovation Team, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
| | - Lanfen Pan
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
- Immunopathology Innovation Team, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
| | - Dan Wu
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
- Immunopathology Innovation Team, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
| | - Liqian Yao
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
| | - Wenqian Jiang
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
| | - Jiarui Min
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China
| | - Song Xu
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China.
- Immunopathology Innovation Team, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China.
| | - Zhiyong Deng
- Department of Pathology, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China.
- Immunopathology Innovation Team, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, China.
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14
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Shi X, Zhao X, Xue J, Jia E. Extracellular vesicle biomarkers in circulation for colorectal cancer detection: a systematic review and meta-analysis. BMC Cancer 2024; 24:623. [PMID: 38778252 PMCID: PMC11110411 DOI: 10.1186/s12885-024-12312-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 04/25/2024] [Indexed: 05/25/2024] Open
Abstract
We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August 2022.Weidentified 48 studies that involved 7727 participants and evaluated 162 plasma/serum individual EV biomarkers including 117 RNAs and 45 proteins, as well as 45 EV biomarker panels for CRC detection. 12 studies evaluated the diagnostic performance of EV biomarkers for early CRC. The summarized sensitivity, specificity, and AUC value of individual EV RNAs and EV RNA panels were 76%, 75%, 0.87 and 82%, 79% and 0.90, respectively. Meanwhile, those of individual EV proteins and EV protein panels were 85%, 84%, 0.92 and 87%, 83%, 0.92, respectively. These results indicated that EV biomarker panels revealed superior diagnostic performance than the corresponding individual biomarkers. In early CRC, EV biomarkers showed available diagnostic value with the sensitivity, specificity, and AUC value of 80%, 75%, and 0.89.In subgroup analyses, EV miRNAs and LncRNAs held similar diagnostic value with the sensitivity, specificity and AUC value of 75%, 78%, 0.90 and 79%, 72%, 0.83, which was highly consistent with the whole EV RNAs. Significantly, the diagnostic values of EV miRNAs in plasma were marginally higher than those based on serum. In detail, the sensitivity, specificity, and AUC values were 79%, 81%, and 0.92 in plasma, as well as 74%, 77%, and 0.88 in serum, respectively. Therefore, circulation EV biomarkers could be considered as a promising biomarker for the early detection of CRC.
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Affiliation(s)
- Xianquan Shi
- Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xinyu Zhao
- Clinical Epidemiology & EBM Unit, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Jinru Xue
- Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
| | - Erna Jia
- Department of Gastroenterology, China-Japan Union Hospital of Jilin University, Changchun, China.
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15
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Rahmati S, Moeinafshar A, Rezaei N. The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk. J Transl Med 2024; 22:452. [PMID: 38741166 PMCID: PMC11092134 DOI: 10.1186/s12967-024-05267-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 04/29/2024] [Indexed: 05/16/2024] Open
Abstract
Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell-cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.
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Affiliation(s)
- Soheil Rahmati
- Student Research Committee, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran
- Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Aysan Moeinafshar
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194, Iran.
- Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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16
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Li X, Zhao X, Xie L, Song X, Song X. Identification of four snoRNAs (SNORD16, SNORA73B, SCARNA4, and SNORD49B) as novel non-invasive biomarkers for diagnosis of breast cancer. Cancer Cell Int 2024; 24:55. [PMID: 38311725 PMCID: PMC10840236 DOI: 10.1186/s12935-024-03237-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 01/20/2024] [Indexed: 02/06/2024] Open
Abstract
BACKGROUND Emerging data point to the critical role of snoRNA in the emergence of different types of cancer, but scarcely in breast cancer (BC). This study aimed to clarify the differential expressions and potential diagnostic value of SNORD16, SNORA73B, SCARNA4, and SNORD49B in BC. METHODS We screened differential snoRNAs in BC tissues and adjacent tissues through SNORic datasets, and then we further verified them in the plasma of BC patients and healthy volunteers by quantitative polymerase chain reaction (qPCR). RESULTS These four snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were considerably more abundant in cancerous tissues than in neighboring tissues in the TCGA database. Their plasma levels were also higher in BC and early-stage BC patients when compared to healthy controls. Furthermore, the ROC curve demonstrated that BC (AUC = 0.7521) and early-stage BC (AUC = 0.7305) might be successfully distinguished from healthy people by SNORD16, SNORA73B, SCARNA4, and SNORD49B. CONCLUSION Plasma snoRNAs: SNORD16, SNORA73B, SCARNA4, and SNORD49B were upregulated in BC and early-stage BC and can be used as potential diagnostic markers for BC and early-stage BC.
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Affiliation(s)
- Xiao Li
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Ji-Yan Road, Jinan, 250117, Shandong Province, China
| | - Xuan Zhao
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Ji-Yan Road, Jinan, 250117, Shandong Province, China
| | - Li Xie
- Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xingguo Song
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Ji-Yan Road, Jinan, 250117, Shandong Province, China
| | - Xianrang Song
- Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
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Torresan S, de Scordilli M, Bortolot M, Di Nardo P, Foltran L, Fumagalli A, Guardascione M, Ongaro E, Puglisi F. Liquid biopsy in colorectal cancer: Onward and upward. Crit Rev Oncol Hematol 2024; 194:104242. [PMID: 38128627 DOI: 10.1016/j.critrevonc.2023.104242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/20/2023] [Accepted: 12/15/2023] [Indexed: 12/23/2023] Open
Abstract
Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide. In recent years, liquid biopsy has emerged as one of the most interesting areas of research in oncology, leading to innovative trials and practical changes in all aspects of CRC management. RNAs and cell free DNA (cfDNA) methylation are emerging as promising biomarkers for early diagnosis. Post-surgical circulating tumour DNA (ctDNA) can aid in evaluating minimal residual disease and personalising adjuvant treatment. In rectal cancer, ctDNA could improve response assessment to neoadjuvant therapy and risk stratification, especially in the era of organ-preservation trials. In the advanced setting, ctDNA analysis offers the opportunity to monitor treatment response and identify driver and resistance mutations more comprehensively than traditional tissue analysis, providing prognostic and predictive information. The aim of this review is to provide a detailed overview of the clinical applications and future perspectives of liquid biopsy in CRC.
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Affiliation(s)
- Sara Torresan
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Marco de Scordilli
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; Department of Medicine, University of Udine, 33100 Udine, Italy.
| | - Martina Bortolot
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Paola Di Nardo
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
| | - Luisa Foltran
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
| | - Arianna Fumagalli
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
| | - Michela Guardascione
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
| | - Elena Ongaro
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy
| | - Fabio Puglisi
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; Department of Medicine, University of Udine, 33100 Udine, Italy
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18
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Mahmoudivar S, Zarredar H, Asadi M, Zafari V, Hashemzadeh S, Farzaneh R, Asvadi Kermani T. Serum miR-23 and miR-150 Profiles as Biomarkers for Predicting Recurrence following Surgical Intervention in Colorectal Cancer Patients. Rep Biochem Mol Biol 2024; 12:540-549. [PMID: 39086590 PMCID: PMC11288239 DOI: 10.61186/rbmb.12.4.540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/26/2024] [Indexed: 08/02/2024]
Abstract
Background MicroRNAs (miRNAs) play pivotal roles in post-transcriptional regulation of gene expression and have emerged as crucial regulators in cancer development, progression, and metastasis. This study aimed to assess the expression profiles of miR-23, miR-223, miR-1246, and miR-150 in serum samples obtained from colorectal cancer (CRC) patients before and three months after surgery, in comparison to a healthy control group, to explore their biomarker potential. Methods A total of 50 blood samples were collected from patients with CRC (pre- and post-surgery), along with 50 samples from healthy controls. The relative expression levels of miR-23, miR-223, miR-1246, and miR-150 in the serum were quantified using quantitative real-time PCR. Results Our findings revealed upregulated expression levels of miR-23, miR-1246, and miR-223, while miR-150 exhibited significant downregulation in the serum of CRC subjects compared to healthy controls. Receiver operating characteristic (ROC) analysis indicated that miR-23 and miR-150 could distinguish CRC cases from controls with relatively high accuracy. Moreover, three months post-surgery, miR-23, miR-1246, and miR-223 serum levels were downregulated, and miR-150 was significantly upregulated. However, no significant correlations were observed between serum levels of the studied genes and the clinical features of our patients. Conclusions The serum levels of miR-23 and miR-150 hold promise as potential biomarkers for the diagnosis and prognosis of CRC.
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Affiliation(s)
- Saeid Mahmoudivar
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Habib Zarredar
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Milad Asadi
- Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey.
| | - Venus Zafari
- Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey.
| | - Shahriyar Hashemzadeh
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Rojin Farzaneh
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Touraj Asvadi Kermani
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Liao W, Deng X, Chen G, Yang J, Li Y, Li L, Zhong L, Tao G, Hou J, Li M, Ding C. MiR-150-5p contributes to unexplained recurrent spontaneous abortion by targeting VEGFA and downregulating the PI3K/AKT/mTOR signaling pathway. J Assist Reprod Genet 2024; 41:63-77. [PMID: 37921969 PMCID: PMC10789717 DOI: 10.1007/s10815-023-02959-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 09/25/2023] [Indexed: 11/05/2023] Open
Abstract
PURPOSE The purpose of this study is to investigate the function of miR-150-5p in URSA. METHOD Twenty-six chorionic villous tissues were collected to examine the expression of miR-150-5p and VEGFA by using quantitative polymerase chain reaction (qPCR) and western blot assay, respectively. Transwell assay was conducted to assess the migration and invasion ability of trophoblast cells. The dual-luciferase reporter assay was applied to determine the relationship between miR-150-5p and VEGFA in vitro. Relevant signaling pathway protein expression level was measured via western blot assay. Signaling transduction inhibitor LY294002 was used to block PI3K/AKT/mTOR signaling pathway. Finally, in vivo the effect of miR-150-5p on embryonic absorption rate was evaluated in mice. RESULTS Clinical samples revealed that miR-150-5p expression was significantly elevated in the villous tissues and serum of URSA patients. Moreover, the overexpressing of miR-150-5p could inhibit both HTR-8/SVneo cell and JAR cell migration, invasion, and restrained PI3K/AKT/mTOR signaling pathway by targeting VEGFA in vitro. This inhibitory effect of miR-150-5p could be reversed by overexpressing the gene of vascular epithelial growth factor A (VEGFA). In contrary, inhibition of miR-150-5p significantly enhanced migration, invasion ability of both HTR-8/SVneo and JAR cells, and also could stimulate PI3K/AKT/mTOR signaling pathway. This promoting effect of miR-150-5p could be ameliorated by LY294002 (PI3K inhibitor). Finally, after miR-150-5p overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. CONCLUSIONS Overall, these findings imply that miR-150-5p is among the key factors that regulate the pathogenesis of URSA.
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Affiliation(s)
- Wenyan Liao
- The First Affiliated Hospital, Department of Gynaecology and Obstetrics, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China
| | - Xin Deng
- The First Affiliated Hospital, Department of Hepatopancreatobiliary Surgery, Hengyang Medical School, University of South China, No. 69, Chuanshan Road, Hengyang, 421001, Hunan, China
| | - Guodong Chen
- The First Affiliated Hospital, Department of Hepatopancreatobiliary Surgery, Hengyang Medical School, University of South China, No. 69, Chuanshan Road, Hengyang, 421001, Hunan, China
| | - Juanli Yang
- The First Affiliated Hospital, Department of Gynaecology and Obstetrics, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Yi Li
- The First Affiliated Hospital, Department of Gynaecology and Obstetrics, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Li Li
- The First Affiliated Hospital, Department of Gynaecology and Obstetrics, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Lili Zhong
- The First Affiliated Hospital, Department of Gynaecology and Obstetrics, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Guangwei Tao
- The First Affiliated Hospital, Department of Hepatopancreatobiliary Surgery, Hengyang Medical School, University of South China, No. 69, Chuanshan Road, Hengyang, 421001, Hunan, China
| | - Jiafeng Hou
- The First Affiliated Hospital, Department of Hepatopancreatobiliary Surgery, Hengyang Medical School, University of South China, No. 69, Chuanshan Road, Hengyang, 421001, Hunan, China
| | - Mujun Li
- Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, 530021, Guangxi, China.
| | - Chengming Ding
- The First Affiliated Hospital, Department of Hepatopancreatobiliary Surgery, Hengyang Medical School, University of South China, No. 69, Chuanshan Road, Hengyang, 421001, Hunan, China.
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Xue VW, Ng SSM, Tsang HF, Wong HT, Leung WW, Wong YN, Wong YKE, Yu ACS, Yim AKY, Cho WCS, Tai WCS, Wong SCC. The non-invasive diagnosis of colorectal cancer via a SOX9-based gene panel. Clin Exp Med 2023; 23:2421-2432. [PMID: 36637582 DOI: 10.1007/s10238-022-00970-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 12/01/2022] [Indexed: 01/14/2023]
Abstract
Colorectal cancer (CRC) threatens human health seriously. Early diagnosis of CRC is critical to improving patient survival. Meanwhile, non-invasive detection through tumor-circulating markers can be an important auxiliary diagnosis. In this study, we performed targeted RNA sequencing in paired tumor and adjacent normal fresh frozen tissues from 68 patients, and we also measured circulating mRNA levels in 4 time-point plasma samples collected before and after operation or chemotherapy. Our results showed that SOX9 (6.73-fold with adjusted p value < 1 × 10-45), MYC (20.59-fold with adjusted p value < 1 × 10-57), and MMP7 (131.94-fold with adjusted p value < 1 × 10-78) highly expressed in tumor compared with adjacent normal tissues. Besides, the circulating mRNA of SOX9 (41.14-fold with adjusted p value < 1 × 10-13) in CRC was significantly higher than in the normal control as well. Moreover, a SOX9-based 9-gene panel (SOX9, GSK3A, FZD4, LEF1, DVL1, FZD7, NFATC1, KRT19, and RUVBL1) showed the non-invasive diagnostic value of CRC (AUC: 0.863 (0.766-0.960), TPR: 0.92, TNR: 0.87). In summary, SOX9 expression consistently increases in tumor and plasma samples from CRC patients, which indicates the important role of SOX9 in CRC progression and its potential in non-invasive diagnosis of CRC.
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Affiliation(s)
- Vivian Weiwen Xue
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China
- Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, International Cancer Center, Department of Pharmacology, Shenzhen University Health Science Center, Shenzhen, China
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China
| | - Simon Siu Man Ng
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Kowloon, Hong Kong Special Administrative Region, China
| | - Hin Fung Tsang
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China
| | - Heong Ting Wong
- Department of Pathology, Kiang Wu Hospital, Santo António, Macau Special Administrative Region, China
| | - Wing Wa Leung
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Kowloon, Hong Kong Special Administrative Region, China
| | - Yee Ni Wong
- Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Kowloon, Hong Kong Special Administrative Region, China
| | - Yin Kwan Evelyn Wong
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China
| | - Allen Chi Shing Yu
- Codex Genetics Limited, Kowloon, Hong Kong Special Administrative Region, China
| | - Aldrin Kay Yuen Yim
- Codex Genetics Limited, Kowloon, Hong Kong Special Administrative Region, China
| | - William Chi Shing Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Special Administrative Region, China
| | - William Chi Shing Tai
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China
| | - Sze Chuen Cesar Wong
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong Special Administrative Region, China.
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Wu L, Xue M, Lai S, Chen J, Lin Y, Ding N, Zhong J, Chen S, Wang L. Hypoxia derived exosomes promote the proliferation and metastasis of colorectal cancer through the regulation of HIF-1α/miR-4299/ZBTB4. Life Sci 2023; 329:121872. [PMID: 37352917 DOI: 10.1016/j.lfs.2023.121872] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 06/14/2023] [Accepted: 06/16/2023] [Indexed: 06/25/2023]
Abstract
AIMS The biological functions of colorectal cancer (CRC) cell derived exosomes responding to hypoxic microenvironment and its underlying mechanisms remain unclear. MAIN METHODS Extracted exosomes were confirmed. CRC cells were incubated with hypoxic and normoxic exosomes and its biological behavior were analyzed. miRNA microarray were conducted. Cells were incubated with miRNAs mimics, inhibitors, or small interfering RNAs; expression of reporter constructs was measured in luciferase assays. Cells were transfected with Lentivirus vectors containing eGFP-miR-4299 overexpression (or ZBTB4 siRNA expression plasmid) and they were injected into BALB/C nude mice subcutaneously or by tail vein and the growth of xenograft tumors or lung metastasis were measured. The clinical significance of ZBTB4 was measured in tumor tissues and adjacent non-tumor tissues. KEY FINDINGS Hypoxic exosomes could tranfer to the recipient normoxic cells and promote the cell proliferation and migration. We found several miRNAs were significantly up-regulated in hypoxic exosomes and the expression levels of miR-4299 increased in both hypoxic cells and hypoxic exosomes. We observed that miR-4299 was upregulated in a HIF-1α dependent way. In addition, ectopic expression of miR-4299 promoted the tumor growth and metastasis in vitro and in vivo. ZBTB4, an identified direct target of miR-4299, could abrogate the effect on tumor growth and distant metastasis. The expression of ZBTB4 were decreased in tumor tissues compared with non-tumor colon tissues from patients. SIGNIFICANCE We demonstrated that in response to hypoxia, CRC cells had an increased production of exosomes. The hypoxia derived exosomes promote the proliferation and metastasis of colorectal cancer by exporting miR-4299 and modulating its target gene ZBTB4.
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Affiliation(s)
- Lunpo Wu
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China
| | - Meng Xue
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China
| | - Sanchuan Lai
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China
| | - Jingyu Chen
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China
| | - Yifeng Lin
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China
| | - Ning Ding
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China
| | - Jing Zhong
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China
| | - Shujie Chen
- Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China; Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
| | - Liangjing Wang
- Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China; Institution of Gastroenterology, Zhejiang University, Hangzhou 310000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
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22
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Cruz-Burgos M, Cortés-Ramírez SA, Losada-García A, Morales-Pacheco M, Martínez-Martínez E, Morales-Montor JG, Servín-Haddad A, Izquierdo-Luna JS, Rodríguez-Martínez G, Ramos-Godínez MDP, González-Covarrubias V, Cañavera-Constantino A, González-Ramírez I, Su B, Leong HS, Rodríguez-Dorantes M. Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis. Cancers (Basel) 2023; 15:4148. [PMID: 37627176 PMCID: PMC10453180 DOI: 10.3390/cancers15164148] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 08/05/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes. This study aims to investigate the potential diagnostic utility of EV-derived microRNAs in liquid biopsies for prostate cancer. By employing microarrays on paraffin-embedded samples, we characterized the microRNA expression profiles in metastatic lymph nodes, non-metastatic lymph nodes, and primary tumor tissues of prostate cancer. Differential expression of microRNAs was observed in metastatic lymph nodes compared to prostate tumors and non-metastatic lymph node tissues. Three microRNAs (miR-140-3p, miR-150-5p, and miR-23b-3p) were identified as differentially expressed between tissue and plasma samples. Furthermore, we evaluated the expression of these microRNAs in exosomes derived from prostate cancer cells and plasma samples. Intriguingly, high Gleason score samples exhibited the lowest expression of miR-150-5p compared to control samples. Pathway analysis suggested a potential regulatory role for miR-150-5p in the Wnt pathway and bone metastasis. Our findings suggest EV-derived miR-150-5p as a promising diagnostic marker for identifying patients with high-grade Gleason scores and detecting metastasis at an early stage.
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Affiliation(s)
- Marian Cruz-Burgos
- Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (M.C.-B.)
| | - Sergio A. Cortés-Ramírez
- Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (M.C.-B.)
| | - Alberto Losada-García
- Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (M.C.-B.)
| | - Miguel Morales-Pacheco
- Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (M.C.-B.)
| | - Eduardo Martínez-Martínez
- Laboratory of Cell Communication and Extracellular Vesicles, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico
| | | | - Alejandro Servín-Haddad
- Urology Department, Hospital General Dr. Manuel Gea Gonzalez, Mexico City 14080, Mexico; (J.G.M.-M.); (A.S.-H.)
| | | | - Griselda Rodríguez-Martínez
- Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (M.C.-B.)
| | | | | | | | - Imelda González-Ramírez
- Departamento de Atención a la Salud, Universidad Autónoma Metropolitana, Mexico City 14387, Mexico
| | - Boyang Su
- Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada
- Biological Sciences Platform, Sunybrook Research Institute, Toronto, ON M4N 3M5, Canada
| | - Hon S. Leong
- Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada
- Biological Sciences Platform, Sunybrook Research Institute, Toronto, ON M4N 3M5, Canada
| | - Mauricio Rodríguez-Dorantes
- Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14610, Mexico; (M.C.-B.)
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23
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Ponomaryova AA, Rykova EY, Solovyova AI, Tarasova AS, Kostromitsky DN, Dobrodeev AY, Afanasiev SA, Cherdyntseva NV. Genomic and Transcriptomic Research in the Discovery and Application of Colorectal Cancer Circulating Markers. Int J Mol Sci 2023; 24:12407. [PMID: 37569782 PMCID: PMC10419249 DOI: 10.3390/ijms241512407] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 07/24/2023] [Accepted: 08/02/2023] [Indexed: 08/13/2023] Open
Abstract
Colorectal cancer (CRC) is the most frequently occurring malignancy in the world. However, the mortality from CRC can be reduced through early diagnostics, selection of the most effective treatment, observation of the therapy success, and the earliest possible diagnosis of recurrences. A comprehensive analysis of genetic and epigenetic factors contributing to the CRC development is needed to refine diagnostic, therapeutic, and preventive strategies and to ensure appropriate decision making in managing specific CRC cases. The liquid biopsy approach utilizing circulating markers has demonstrated its good performance as a tool to detect the changes in the molecular pathways associated with various cancers. In this review, we attempted to brief the main tendencies in the development of circulating DNA and RNA-based markers in CRC such as cancer-associated DNA mutations, DNA methylation changes, and non-coding RNA expression shifts. Attention is devoted to the existing circulating nucleic acid-based CRC markers, the possibility of their application in clinical practice today, and their future improvement. Approaches to the discovery and verification of new markers are described, and the existing problems and potential solutions for them are highlighted.
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Affiliation(s)
- Anastasia A. Ponomaryova
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634009 Tomsk, Russia
| | - Elena Yu. Rykova
- Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
- Department of Engineering Problems of Ecology, Novosibirsk State Technical University, 630087 Novosibirsk, Russia
| | - Anastasia I. Solovyova
- Department of Biochemistry, Medico-Biological Faculty, Siberian State Medical University, 634050 Tomsk, Russia
| | - Anna S. Tarasova
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634009 Tomsk, Russia
| | - Dmitry N. Kostromitsky
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634009 Tomsk, Russia
| | - Alexey Yu. Dobrodeev
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634009 Tomsk, Russia
| | - Sergey A. Afanasiev
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634009 Tomsk, Russia
| | - Nadezhda V. Cherdyntseva
- Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634009 Tomsk, Russia
- Faculty of Chemistry, National Research Tomsk State University, 634050 Tomsk, Russia
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Mishra A, Bharti PS, Rani N, Nikolajeff F, Kumar S. A tale of exosomes and their implication in cancer. Biochim Biophys Acta Rev Cancer 2023; 1878:188908. [PMID: 37172650 DOI: 10.1016/j.bbcan.2023.188908] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/15/2023]
Abstract
Cancer is a cause of high deaths worldwide and also a huge burden for the health system. Cancer cells have unique properties such as a high rate of proliferation, self-renewal, metastasis, and treatment resistance, therefore, the development of novel diagnoses of cancers is a tedious task. Exosomes are secreted by virtually all cell types and have the ability to carry a multitude of biomolecules crucial for intercellular communication, hence, contributing a crucial part in the onset and spread of cancer. These exosomal components can be utilized in the development of markers for diagnostic and prognostic purposes for various cancers. This review emphasized primarily the following topics: exosomes structure and functions, isolation and characterization strategies of exosomes, the role of exosomal contents in cancer with a focus in particular on noncoding RNA and protein, exosomes, and the cancer microenvironment interactions, cancer stem cells, and tumor diagnosis and prognosis based on exosomes.
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Affiliation(s)
- Abhay Mishra
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Prahalad Singh Bharti
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Neerja Rani
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Fredrik Nikolajeff
- Department of Health, Education, and Technology, Lulea University of Technology, 97187, Sweden
| | - Saroj Kumar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India; Department of Health, Education, and Technology, Lulea University of Technology, 97187, Sweden.
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25
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Shi YJ, Fang YX, Tian TG, Chen WP, Sun Q, Guo FQ, Gong PQ, Li CM, Wang H, Hu ZQ, Li XX. Discovery of extracellular vesicle-delivered miR-185-5p in the plasma of patients as an indicator for advanced adenoma and colorectal cancer. J Transl Med 2023; 21:421. [PMID: 37386465 PMCID: PMC10308673 DOI: 10.1186/s12967-023-04249-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 06/05/2023] [Indexed: 07/01/2023] Open
Abstract
BACKGROUND We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). METHODS We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. RESULTS We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. CONCLUSION EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).
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Affiliation(s)
- Yun-Jie Shi
- Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200003, China
- Department of Anorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200433, China
| | - Yu-Xiang Fang
- State Key Laboratory of Systems Medicine for Cancer, Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
| | - Tong-Guan Tian
- Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China
| | - Wei-Ping Chen
- Institute of Basic Medicine and Cancer (IBMC), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Qiang Sun
- Department of Gastrointestinal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200003, China
| | - Fang-Qi Guo
- Department of Ultrasound, Shanghai Fourth People' Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Pi-Qing Gong
- Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200003, China
| | - Chun-Mei Li
- Institute of Basic Medicine and Cancer (IBMC), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China
| | - Hao Wang
- Department of Anorectal Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200433, China.
| | - Zhi-Qian Hu
- Department of Anorectal Surgery, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200003, China.
- Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
| | - Xin-Xing Li
- Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
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26
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Jafari A, Karimabadi K, Rahimi A, Rostaminasab G, Khazaei M, Rezakhani L, Ahmadi jouybari T. The Emerging Role of Exosomal miRNAs as Biomarkers for Early Cancer Detection: A Comprehensive Literature Review. Technol Cancer Res Treat 2023; 22:15330338231205999. [PMID: 37817634 PMCID: PMC10566290 DOI: 10.1177/15330338231205999] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 09/10/2023] [Accepted: 09/13/2023] [Indexed: 10/12/2023] Open
Abstract
A significant number of cancer-related deaths are recorded globally each year, despite attempts to cure this illness. Medical science is working to develop new medication therapies as well as to find ways to identify this illness as early as possible, even using noninvasive techniques. Early detection of cancer can greatly aid its treatment. Studies into cancer diagnosis and therapy have recently shifted their focus to exosome (EXO) biomarkers, which comprise numerous RNA and proteins. EXOs are minuscule goblet vesicles that have a width of 30 to 140 nm and are released by a variety of cells, including immune, stem, and tumor cells, as well as bodily fluids. According to a growing body of research, EXOs, and cancer appear to be related. EXOs from tumors play a role in the genetic information transfer between tumor and basal cells, which controls angiogenesis and fosters tumor development and spread. To identify malignant activities early on, microRNAs (miRNAs) from cancers can be extracted from circulatory system EXOs. Specific markers can be used to identify cancer-derived EXOs containing miRNAs, which may be more reliable and precise for early detection. Conventional solid biopsy has become increasingly limited as precision and personalized medicine has advanced, while liquid biopsy offers a viable platform for noninvasive diagnosis and prognosis. Therefore, the use of body fluids such as serum, plasma, urine, and salivary secretions can help find cancer biomarkers using technologies related to EXOs.
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Affiliation(s)
- Ali Jafari
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Keyvan Karimabadi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Aso Rahimi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Gelavizh Rostaminasab
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mozafar Khazaei
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Leila Rezakhani
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Touraj Ahmadi jouybari
- Clinical Research Development Center, Imam Khomeini and Mohammad Kermanshahi and Farabi Hospitals, Kermanshah University of Medical Sciences, Kermanshah, Iran
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27
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Zhao Y, Song X, Song X, Xie L. Identification of Diagnostic Exosomal LncRNA-miRNA-mRNA Biomarkers in Colorectal Cancer Based on the ceRNA Network. Pathol Oncol Res 2022; 28:1610493. [PMID: 36185995 PMCID: PMC9522904 DOI: 10.3389/pore.2022.1610493] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 09/08/2022] [Indexed: 12/24/2022]
Abstract
Background: Colorectal cancer (CRC) is currently the fourth most common cancer worldwide. The roles of exosomal competing endogenous RNAs (ceRNAs) in CRC remain unclear. In this study, we constructed an exosomal ceRNA network to identify the core ceRNAs and investigate the diagnostic biomarkers in CRC.Methods and Patients: Serum exosomes were isolated from four CRC patients and two healthy donors by ultracentrifugation, and then subjected to RNA isolation, sequencing and microarray. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were performed to identify functional enrichment implications of differentially expressed exosomal mRNAs. TargetScan and miRanda were used for identifying the miRNA-mRNA and miRNA-LncRNA interactions. The predicted lncRNAs and mRNAs were intersected with the differentially expressed genes, for which the screening criterion was fold change >1.5 in the microarray. Differentially expressed exosomal miRNAs were identified in the GSE71008 dataset, and differentially expressed mRNAs (DEmRNAs) were further summarized from The Cancer Genome Atlas (TCGA) database.Results: A total of 1186 exosomal DEmRNAs, 2088 exosomal DElncRNAs and 29 exosomal miRNAs were detected in CRC patients compared to the healthy donors. Functional enrichment analysis suggested that exosomal DEmRNAs might participate in pathways related to carcinogenesis and development of cancer. An exosomal ceRNA regulatory network of CRC was constructed based on 40 lncRNAs, two miRNAs, and five mRNAs. Exosomal miR-150-5p and miR-10b-5p expression levels were increased in healthy donors compared with CRC patients in the GSE71008 dataset, and five DEmRNAs (TOMM70A, RBM48, BEND3, RHOBTB1, and ADAMTS2) were significantly upregulated in TCGA database. Two potential exosomal regulatory axes of lncRNA G016261-miR-150-5p-RBM48 and lncRNA XLOC_011677-miR-10b-5p-BEND3 were identified from the network.Conclusion: The current study revealed potential molecular biological regulation pathways and diagnostic biomarkers through the exosomal ceRNA regulatory network.
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Investigating the Role of Circulating miRNAs as Biomarkers in Colorectal Cancer: An Epidemiological Systematic Review. Biomedicines 2022; 10:biomedicines10092224. [PMID: 36140324 PMCID: PMC9496335 DOI: 10.3390/biomedicines10092224] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/01/2022] [Accepted: 09/03/2022] [Indexed: 11/20/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. Primary and secondary preventions are key to reducing the global burden. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and to be related to cancer risk factors, such as obesity and inflammation. We conducted a systematic review and meta-analysis to identify circulating miRNAs related to CRC diagnosis that could be selected as biomarkers in a meet-in-the-middle analysis. Forty-four studies were included in the systematic review and nine studies in the meta-analysis. The pooled sensitivity and specificity of miR-21 for CRC diagnosis were 77% (95% CI: 69–84) and 82% (95% CI: 70–90), respectively, with an AUC of 0.86 (95% CI: 0.82–0.88). Several miRNAs were found to be dysregulated, distinguishing patients with CRC from healthy controls. However, little consistency was present across the included studies, making it challenging to identify specific miRNAs, which were consistently validated. Understanding the mechanisms by which miRNAs become biologically embedded in cancer initiation and promotion may help better understand cancer pathways to develop more effective prevention strategies and therapy approaches.
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29
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Gujrati H, Ha S, Waseem M, Wang BD. Downregulation of miR-99b-5p and Upregulation of Nuclear mTOR Cooperatively Promotes the Tumor Aggressiveness and Drug Resistance in African American Prostate Cancer. Int J Mol Sci 2022; 23:9643. [PMID: 36077039 PMCID: PMC9455949 DOI: 10.3390/ijms23179643] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
Mammalian target of rapamycin (mTOR) regulates various fundamental cellular events including cell proliferation, protein synthesis, metabolism, apoptosis, and autophagy. Tumor suppressive miR-99b-5p has been implicated in regulating PI3K/AKT/mTOR signaling in a variety of types of cancer. Our previous study suggested the reciprocal miR-99b-5p/MTOR (downregulated/upregulated) pairing as a key microRNA-mRNA regulatory component involved in the prostate cancer (PCa) disparities. In this study, we further validated the expression profiles of mTOR and miR-99b-5p in the PCa, colon, breast, and lung cancer specimens and cell lines. The immunohistochemistry (IHC), immunofluorescence, Western blot, and RT-qPCR assays have confirmed that mTOR is upregulated while miR-99b-5p is downregulated in different patient cohorts and a panel of cancer cell lines. Intriguingly, elevated nuclear mTOR expression was observed in African American PCa and other advanced cancers. Transfection of the miR-99b-5p mimic resulted in a significant reduction in nuclear mTOR and androgen receptor (AR), while a slight/moderate to no decrease in cytoplasmic mTOR and AR in PCa and other cancer cells, suggesting that miR-99b-5p inhibits mTOR and AR expression and their nuclear translocation. Moreover, overexpression of miR-99b-5p targets/inhibits AR-mTOR axis, subsequently initiating cell apoptosis and sensitizing docetaxel-induced cytotoxicity in various cancers. In conclusion, our data suggest that reciprocal miR-99b-5p/nuclear mTOR pairing may be a more precise diagnostic/prognostic biomarker for aggressive PCa, than miR-99b-5p/MTOR pairing or mTOR alone. Targeting the AR-mTOR axis using miR-99b-5p has also been suggested as a novel therapeutic strategy to induce apoptosis and overcome chemoresistance in aggressive PCa.
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Affiliation(s)
- Himali Gujrati
- Department of Pharmaceutical Sciences, University of Maryland Eastern Shore School of Pharmacy, Princess Anne, MD 21853, USA
| | - Siyoung Ha
- Department of Pharmaceutical Sciences, University of Maryland Eastern Shore School of Pharmacy, Princess Anne, MD 21853, USA
| | - Mohammad Waseem
- Department of Pharmaceutical Sciences, University of Maryland Eastern Shore School of Pharmacy, Princess Anne, MD 21853, USA
| | - Bi-Dar Wang
- Department of Pharmaceutical Sciences, University of Maryland Eastern Shore School of Pharmacy, Princess Anne, MD 21853, USA
- Hormone Related Cancers Program, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
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Selvam M, Bandi V, Ponne S, Ashok C, Baluchamy S. microRNA-150 targets major epigenetic repressors and inhibits cell proliferation. Exp Cell Res 2022; 415:113110. [DOI: 10.1016/j.yexcr.2022.113110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 03/06/2022] [Accepted: 03/20/2022] [Indexed: 11/29/2022]
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31
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Zhou H, Zhu L, Song J, Wang G, Li P, Li W, Luo P, Sun X, Wu J, Liu Y, Zhu S, Zhang Y. Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer. Mol Cancer 2022; 21:86. [PMID: 35337361 PMCID: PMC8951719 DOI: 10.1186/s12943-022-01556-2] [Citation(s) in RCA: 142] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 03/02/2022] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called “liquid biopsy” has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.
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Affiliation(s)
- Hui Zhou
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.,Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Liyong Zhu
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Jun Song
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Guohui Wang
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Pengzhou Li
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Weizheng Li
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Ping Luo
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Xulong Sun
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Jin Wu
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Yunze Liu
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Shaihong Zhu
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, China.
| | - Yi Zhang
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
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Jorgensen BG, Ro S. MicroRNAs and 'Sponging' Competitive Endogenous RNAs Dysregulated in Colorectal Cancer: Potential as Noninvasive Biomarkers and Therapeutic Targets. Int J Mol Sci 2022; 23:2166. [PMID: 35216281 PMCID: PMC8876324 DOI: 10.3390/ijms23042166] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 01/28/2022] [Accepted: 02/02/2022] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer.
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Affiliation(s)
| | - Seungil Ro
- Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA;
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Chen Y, Liu H, Ning S, Wei C, Li J, Wei W, Zhang L. The High Ratio of the Plasma miR-96/miR-99b Correlated With Poor Prognosis in Patients With Metastatic Colorectal Cancer. Front Mol Biosci 2022; 8:799060. [PMID: 35047559 PMCID: PMC8762210 DOI: 10.3389/fmolb.2021.799060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 12/01/2021] [Indexed: 12/18/2022] Open
Abstract
Object: This study aims to clarify the expression of plasma miRNA in CRC patients, and to clarify the potential use of these miRNAs in diagnosis and prognosis, and to establish a prognostic model to initially explore its clinical value. Methods: We detected the expression of 6 miRNAs in normal colon epithelial cell lines and colorectal cancer cell lines by qRT-PCR and they were validated in the tissues of three subtypes: 20 healthy subjects, 41 pCRC and 49 mCRC patients. COX regression and ROC analyses use to evaluate the diagnostic and prognostic efficacy of candidate miRNAs. Subsequently, we initially established a nomogram prognostic model. MiRNA is also used to construct miRNA-mRNA interaction network and PPI network modules. Results: Five miRNAs showed significant differential expression in pCRC, mCRC patients and normal groups. ROC analysis showed that CEA, miR-96, miR-99b and miR-96/miR-99b are distinguishable from pCRC and mCRC patients, with AUC ranging from 0.65 to 0.91; among them, the ratio of miR-96/miR-99b is stronger than any diagnostic indicators, such as CEA and CA125. Multivariate survival analysis identified miR-96, miR-99b, N stage, M stage and clinical stage as independent prognostic indicators of mCRC. The nomogram based on these 5 characteristics has satisfactory prognostic values. Conclusion: Our data indicate that plasma miR-96/miR-99b can be used as a promising biomarker for early detection of mCRC patients; our nomogram has a promising evaluation value.
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Affiliation(s)
- Yi Chen
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Haizhou Liu
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China.,Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning, China
| | - Shufang Ning
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Changhong Wei
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jilin Li
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Wene Wei
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Litu Zhang
- Department of Research, Guangxi Medical University Cancer Hospital, Nanning, China.,Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning, China
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Jiang S, Chen H, He K, Wang J. Human bone marrow mesenchymal stem cells-derived exosomes attenuated prostate cancer progression via the miR-99b-5p/IGF1R axis. Bioengineered 2022; 13:2004-2016. [PMID: 35030978 PMCID: PMC8973722 DOI: 10.1080/21655979.2021.2009416] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
MicroRNA-99b-5p (miR-99b-5p) has been shown to be enriched in serum exosomes of prostate cancer (PCa) patients treated with radiotherapy, while its function in PCa progression remains unclear. The expression levels of miR-99b-5p in PCa tissues, cancer cell lines and human bone marrow mesenchymal stem cells (HBMSCs), as well as HBMSCs-derived exosomes were assessed by quantitative real-time PCR (qRT-PCR). MiR-99b-5p mimics or inhibitor was transfected into HBMSCs, and HBMSCs-derived exosomes with abnormal expression of miR-99b-5p were used to stimulate PCa cell-line LNCaP cells. Cell proliferative rate was evaluated using Cell Counting Kit-8 (CCK-8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) staining assays. Cell migration and invasion were analyzed by Transwell assay. The epithelial-mesenchymal transition (EMT) was evaluated by detecting EMT-related markers using Western blot analysis. The animal model was constructed to confirm the function of miR-99b-5p in vivo. The expression levels of MiR-99b-5p were decreased in PCa tissues and cell lines, while elevated in HBMSCs-derived exosomes. HBMSCs-derived exosomes significantly inhibited cell malignant phenotypes of PCa cells, and miR-99b-5p mimics transfected HBMSCs further enhanced the inhibitory effects of HBMSCs on PCa progression. In addition, miR-99b-5p inhibitor transfected HBMSCs-derived exosomes promoted the progression of PCa in vitro. Insulin-like growth factor 1 receptor (IGF1R) was identified as a downstream target of miR-99b-5p. Moreover, miR-99b-5p mimics transfected HBMSCs obviously inhibited tumor progression by downregulating IGF1R in animal model in vivo. Our results demonstrated that HBMSCs could attenuate PCa progression, and exosomal miR-99b-5p and IGF1R participated in the regulatory process, contributing to our understanding of the pathogenic mechanism of PCa.
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Affiliation(s)
- Shichun Jiang
- Department of Urology, Mianyang Central Hospital, Mianyang City, Sichuan Province, PR. China
| | - Haiyu Chen
- Department of Surgery, Haikou Hospital of Traditional Chinese Medicine, Haikou City, Hainan Province, PR. China
| | - Kai He
- Department of Urology, Mianyang Central Hospital, Mianyang City, Sichuan Province, PR. China
| | - Juan Wang
- Department of Surgery, Haikou Hospital of Traditional Chinese Medicine, Haikou City, Hainan Province, PR. China
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Chang WA, Tsai MJ, Hung JY, Wu KL, Tsai YM, Huang YC, Chang CY, Tsai PH, Hsu YL. miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells. Cancers (Basel) 2021; 13:cancers13246252. [PMID: 34944871 PMCID: PMC8699319 DOI: 10.3390/cancers13246252] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/09/2021] [Accepted: 12/10/2021] [Indexed: 12/28/2022] Open
Abstract
Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.
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Affiliation(s)
- Wei-An Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (W.-A.C.); (M.-J.T.); (J.-Y.H.); (K.-L.W.); (Y.-M.T.)
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Ming-Ju Tsai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (W.-A.C.); (M.-J.T.); (J.-Y.H.); (K.-L.W.); (Y.-M.T.)
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Jen-Yu Hung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (W.-A.C.); (M.-J.T.); (J.-Y.H.); (K.-L.W.); (Y.-M.T.)
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 801, Taiwan
| | - Kuan-Li Wu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (W.-A.C.); (M.-J.T.); (J.-Y.H.); (K.-L.W.); (Y.-M.T.)
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 801, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (Y.-C.H.); (P.-H.T.)
| | - Ying-Ming Tsai
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (W.-A.C.); (M.-J.T.); (J.-Y.H.); (K.-L.W.); (Y.-M.T.)
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
| | - Yung-Chi Huang
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (Y.-C.H.); (P.-H.T.)
| | - Chao-Yuan Chang
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan;
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (Y.-C.H.); (P.-H.T.)
- Department of Anatomy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Pei-Hsun Tsai
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (Y.-C.H.); (P.-H.T.)
| | - Ya-Ling Hsu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (Y.-C.H.); (P.-H.T.)
- Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Correspondence: ; Tel.: +886-7-312-1101 (ext. 2136-26)
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Wang L, Song X, Yu M, Niu L, Zhao Y, Tang Y, Zheng B, Song X, Xie L. Serum exosomal miR-377-3p and miR-381-3p as diagnostic biomarkers in colorectal cancer. Future Oncol 2021; 18:793-805. [PMID: 34854318 DOI: 10.2217/fon-2021-1130] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Aim: This study aimed to identify specific and sensitive exosomal miRNAs in diagnosing patients with colorectal cancer (CRC). Methods: Serum exosomes were isolated from 175 CRC patients and 172 healthy donors by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was detected by qPCR and the results analyzed by receiver operating characteristic analysis to illuminate the diagnostic accuracy. Results: Both exosomal miR-377-3p and miR-381-3p were downregulated in CRC patients as well as in early-stage patients compared with healthy donors; they could serve as circulating biomarkers of diagnosis, including early diagnosis, for CRC, possessing favorable diagnostic efficiency. Conclusion: Exosomal miR-377-3p and miR-381-3p levels were downregulated in CRC patients and may be useful as novel and specific biomarkers for the diagnosis of CRC, especially early-stage CRC.
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Affiliation(s)
- Li Wang
- Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
| | - Xingguo Song
- Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
| | - Miao Yu
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR, China
| | - Limin Niu
- Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
| | - Yajing Zhao
- Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
| | - Youyong Tang
- Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
| | - Baibing Zheng
- Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
| | - Xianrang Song
- Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
| | - Li Xie
- Department of Clinical Laboratory, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR, China
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Dang Y, Zhang S, Wang Y, Zhao G, Chen C, Jiang W. State-of-the-Art: Exosomes in Colorectal Cancer. Curr Cancer Drug Targets 2021; 22:2-17. [PMID: 34758717 DOI: 10.2174/1568009621666211110094442] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 08/06/2021] [Accepted: 09/09/2021] [Indexed: 11/22/2022]
Abstract
Colorectal cancer (CRC) has a high prevalence and mortality rate, globally. To date, the progression mechanisms of CRC are still elusive. Exosomes (~100 nm in diameter) correspond to a subset of extracellular vesicles formed by an array of cancerous cells and stromal cells. These particular nanovesicles carry and transmit bioactive molecules, like proteins, lipids, and genetic materials, which mediate the crosstalk between cancer cells and the microenvironment. Accumulating evidence has shown the decisive functions of exosomes in the development, metastasis, and therapy resistance of CRC. Furthermore, some recent studies have also revealed the abilities of exosomes to function as either biomarkers or therapeutic targets for CRC. This review focuses on the specific mechanisms of exosomes in regulating CRC progression, and summarizes the potential clinical applications of exosomes in the diagnosis and therapy of CRC.
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Affiliation(s)
- Yan Dang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing. China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing. China
| | - Yongjun Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing. China
| | - Guiping Zhao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing. China
| | - Chuyan Chen
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing. China
| | - Wei Jiang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing. China
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Chen X, Li R, Li X, Peng X, Zhang C, Liu K, Huang G, Lai Y. Identification of a four-microRNA panel in serum for screening renal cell carcinoma. Pathol Res Pract 2021; 227:153625. [PMID: 34628264 DOI: 10.1016/j.prp.2021.153625] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 09/17/2021] [Accepted: 09/18/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND The aim of the study was to identify serum microRNAs (miRNAs) as potential biomarkers for screening renal cell carcinoma. METHODS The study was divided into three stages, including screening stage, training stage, and validation stage. In the screening stage, we examined the expression of 30 serum miRNAs from healthy controls (HCs) and renal cell carcinoma (RCC) patients. We further studied the dysregulated miRNAs in training (30 RCC and 26 HCs) and validation (73 RCC and 80 HCs) stages. We estimated the diagnostic value of miRNAs by receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Finally, bioinformatics analysis were performed towards target genes of differentially expressed miRNAs. RESULTS Six serum miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-150-5p, miR-145-5p and miR-146a-5p) in RCC patients were obviously differentially expressed compared to those in HCs in training stage and validation stage. To increase diagnostic value, we combined these six serum miRNAs and made a four-microRNA (miR-21-5p, miR-150-5p, miR-145-5p and miR-146a-5p) panel, and AUC of the panel was 0.938 (95% CI: 0.889-0.971; sensitivity=90.79%, specificity=93.75%). The genes targeted by these miRNAs were suggested that they may be involved in the process of cancers by the bioinformatics analysis. CONCLUSIONS Our study was performing a four-microRNA panel in serum for screening enal cell carcinoma. The four-miRNA panel (miR-21-5p, miR-150-5p, miR-145-5p and miR-146a-5p) may be perform as a biomarker without invasiveness for RCC screening.
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Affiliation(s)
- Xuan Chen
- Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China
| | - Rongkang Li
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; Anhui Medical University, Hefei, Anhui 230032, China
| | - Xinji Li
- Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China
| | - Xiqi Peng
- Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China
| | - Chunduo Zhang
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China
| | - Kaihao Liu
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China; Anhui Medical University, Hefei, Anhui 230032, China
| | - Guocheng Huang
- Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China
| | - Yongqing Lai
- Department of Urology, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, PR China.
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Circulating exosomal miRNAs and cancer early diagnosis. Clin Transl Oncol 2021; 24:393-406. [PMID: 34524618 DOI: 10.1007/s12094-021-02706-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 08/31/2021] [Indexed: 12/14/2022]
Abstract
Microribonucleic acids (miRNAs) are small non-coding ribonucleic acids (ncRNAs), which can affect recognition of homologous sequences and interfere with transcription. It plays key roles in the initiation, development, resistance, metastasis or recurrence of cancers. Identifying circulatory indicators will positively improve the prognosis and quality of life of patients with early cancer. Previous studies have shown that miRNA is highly involved in cancer. In addition, miRNA derived from cancers can be encapsulated as exosomes and further extracted into circulatory systems to realize malignant functions. It indicates that circulating exosome-derived miRNAs have the potential to replace conventional biomarkers as cancer derived exosomes carrying miRNAs can be identified by specific markers and might be more stable and accurate for early diagnosis.
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Xu N, Guo R, Yang X, Li N, Yu J, Zhang P. Exosomes-mediated tumor treatment: One body plays multiple roles. Asian J Pharm Sci 2021; 17:385-400. [PMID: 35782325 PMCID: PMC9237599 DOI: 10.1016/j.ajps.2021.08.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 08/20/2021] [Accepted: 08/29/2021] [Indexed: 02/06/2023] Open
Abstract
Exosomes are vesicles secreted by a variety of living cells, containing proteins, RNA and other components, which are nanoscale capsules commonly existed in the body. Exosomes play important roles in a variety of physiological and pathological processes by participating in material and information exchange between cells, which can play multiple roles in tumor treatment. On the one hand, exosomes can be used as carriers and biomarkers, participate in the apoptosis signaling pathway and improve chemotherapy resistance, thus playing beneficial roles in tumor treatment. On the other hand, exosomes play unfavorable roles in tumor treatment. Tumor cell exosomes contain PD-L1, which is a nuclear weapon for tumor growth, metastasis, and immunosuppression. In addition, exosomes can not only promote the epithelial-mesenchymal transition process, tumor angiogenesis and chemoresistance, but also participate in the autocrine pathway. In this review, the multiple roles of exosomes and their prospects in the treatment of tumor were reviewed in detail.
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Luo Y, Gui R. Circulating exosomal circFoxp1 confers cisplatin resistance in epithelial ovarian cancer cells. J Gynecol Oncol 2021; 31:e75. [PMID: 32808501 PMCID: PMC7440976 DOI: 10.3802/jgo.2020.31.e75] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 04/29/2020] [Accepted: 05/25/2020] [Indexed: 01/17/2023] Open
Abstract
Objective Early detection and treatment are particularly important to epithelial ovarian cancer (EOC). Studies have shown that circular RNA (circRNA) dysregulation is associated with the proliferation and metastasis of ovarian cancer cells. This study focused on the role of serum exosomal circular forkhead box protein P1 (circFoxp1) on survival outcome and cisplatin (DDP) resistance in patients with EOC. Methods Quantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8, luciferase reporter assay, RNA immunoprecipitation, tumor xenograft in nude mice, and bioinformatic analysis were performed. Results Circulating exosomal circFoxp1 was significantly increased in patients with EOC, especially in DDP-resistant EOC patients. circFoxp1 expression was positively associated with International Federation of Gynecology and Obstetrics stage, primary tumor size, lymphatic metastasis, distant metastasis, residual tumor diameter, and clinical response. Exosomal circFoxp1 also was an independent factor predicting survival and disease recurrence in patients with EOC. Overexpression of circFoxp1 could promote cell proliferation and confer DDP resistance, while knockdown of circFoxp1 could inhibit cell proliferation and enhance DDP sensitivity in vitro and in vivo. In addition, miR-22 and miR-150-3p mimic treatment attenuated circFoxp1-meadiated DDP resistance, while miR-22 and miR-150-3p inhibitor treatment enhanced DDP resistance that mitigated by circFoxp1 knockdown. Furthermore, circFoxp1 positively regulated the expression of CCAAT enhancer binding protein gamma (CEBPG) and formin like 3 (FMNL3) through miR-22 and miR-150-3p. Conclusions circFoxp1 is an oncogene in EOC cells and can confer DDP resistance to EOC cells. Circulating exosomal circFoxp1 can be used as a biomarker and potential therapeutic target for EOC.
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Affiliation(s)
- Yanwei Luo
- Department of Blood Transfusion, the Third Xiangya Hospital of Central South University, Changsha, China
| | - Rong Gui
- Department of Blood Transfusion, the Third Xiangya Hospital of Central South University, Changsha, China.
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Zhang B, Yang S, Wang J. Circ_0084615 is an oncogenic circular RNA in colorectal cancer and promotes DNMT3A expression via repressing miR-599. Pathol Res Pract 2021; 224:153494. [PMID: 34091391 DOI: 10.1016/j.prp.2021.153494] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 05/15/2021] [Accepted: 05/20/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND Circular RNAs (circRNAs) are implicated in modulating cancer progression, exerting a pro- or anti-cancer effect. This work is aimed to probe the biological function of circ_0084615 in colorectal cancer (CRC) and its underlying mechanism. METHODS Circ_0084615 was selected from two circRNA microarray datasets (GSE138589 and GSE142837). Circ_0084615, microRNA (miR)-599 and DNA methyltransferases 3A (DNMT3A) mRNA expression in CRC tissues and cell lines were examined by qRT-PCR. The relationship between circ_0084615 expression level and clinical features were analyzed with chi-square test. Circ_0084615 knockdown model was constructed by siRNA in two CRC cell lines. The biological functions of circ_0084615 in CRC cells were evaluated by CCK-8 and Transwell experiments. The effect of circ_0084615 on CRC cell metastasis in vivo was examined with lung metastasis model of nude mice. Dual luciferase reporter gene assay was used to determine whether circ_0084615 and miR-599, and miR-599 and DNMT3A interacted with each other. Western blot was employed to examine the regulatory effects of circ_0084615 and miR-599 on DNMT3A protein expression in CRC cells. RESULTS Circ_0084615 was up-regulated in CRC and was correlated with poor overall survival rate and advanced clinical stage of CRC patients. Functional assays validated that depletion of circ_0084615 impeded CRC cell proliferation, migration and invasion. Circ_0084615 acted as a molecular sponge for miR-599 to repress its expression. DNMT3A was a downstream target of miR-599. Functional compensation experiments showed that miR-599 inhibitors partially counteracted the the biological effects of silencing circ_0084615 on CRC cells. CONCLUSIONS Circ_0084615 is a tumor-promoting circRNA in CRC that functions as a competing endogenous RNA to regulate DNMT3A expression via sponging miR-599. Our research provides a potential therapeutic target for CRC patients.
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Affiliation(s)
- Baogen Zhang
- Department of Chinese Medicine, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China
| | - Shu Yang
- Department of Chinese Medicine, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, Fujian, China
| | - Junping Wang
- Department of Gastroenterology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Futian District, Shenzhen, 518036, Guangdong, China.
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Umwali Y, Yue CB, Gabriel ANA, Zhang Y, Zhang X. Roles of exosomes in diagnosis and treatment of colorectal cancer. World J Clin Cases 2021; 9:4467-4479. [PMID: 34222415 PMCID: PMC8223826 DOI: 10.12998/wjcc.v9.i18.4467] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/15/2021] [Accepted: 05/06/2021] [Indexed: 02/06/2023] Open
Abstract
Exosomes are extracellular vesicles that mediate intercellular communication. They contain different molecules, such as DNA, RNA, lipid, and protein, playing essential roles in the pathogenesis of colorectal cancer (CRC). Exosomes derived from CRC are implicated in tumorigenesis, chemotherapy resistance, and metastasis. Besides, they can enhance CRC progression by increasing tumor cell proliferation, reducing apoptosis mechanistically through altering particular essential regulatory genes, or controlling several signaling pathways. Therefore, exosomes derived from CRC are essential biomarkers and can be used in the diagnosis. Indeed, it is crucial to understand the role of exosomes in CRC, which is necessary to develop diagnostic and therapeutic strategies for early detection and treatment. In the present review, we discuss the roles of exosomes in the diagnosis and treatment of CRC.
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Affiliation(s)
- Yvette Umwali
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Cong-Bo Yue
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Abakundana Nsenga Ariston Gabriel
- Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
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El Kadmiri N. Advances in Early Detection of Colorectal Cancer: A Focus on Non-invasive Biomarkers. Curr Drug Targets 2021; 22:1043-1053. [PMID: 33655856 DOI: 10.2174/1389450122666210303100048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 12/07/2020] [Accepted: 12/09/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Currently, colonoscopy remains the gold standard diagnostic test for CRC detection. Nonetheless, this technique is invasive and expensive. Remarkable ongoing strategies are focusing on the development of affordable methods to diagnose CRC at earlier stages. The introduction of suitable noninvasive, sensitive and specified diagnostic tests for early CRC detection by employing biomarker analysis seems to be a fundamental need to reduce the numbers of unnecessary colonoscopies. In this review, we provide an overview of single- and multi-panel biomarkers (Genomic markers, transcriptome markers, proteomic markers, inflammatory markers, and microbiome markers) encompassing noninvasive tests in blood and stool for early CRC detection. METHODS A bibliographic search using PubMed/Medline, Web of Science, and EBSCOhost databases was performed to find relevant published studies over the last 6 years. Forty-three pertinent studies were included in this review. RESULTS The primary outcome highlights the sensitivity and specificity of single diagnostic biomarkers studied in blood or stool. The secondary outcome reveals the sensitivity and specificity of the biomarkers panel (combinations) in blood or stool. While some markers show better performance, others are not suitable for screening purposes. CONCLUSION There is a need to adjust experimental and analytical tests that can interfere with a robust result to replace or supplement those markers that are currently in use. Nevertheless, robust verification and validation with large clinical cohorts are needed for successful noninvasive tests that can fulfill the role of colonoscopy.
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Affiliation(s)
- Nadia El Kadmiri
- Molecular Engineering, Valorization and Environment Team, Polydisciplinary Faculty of Taroudant, IBN ZOHR University, Taroudannt, Morocco
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Francone E, Gentilli S, Santori G, Stabilini C, Fornaro R, Frascio M. MicroRNAs differential expression profile in metastatic colorectal cancer: A pilot study with literature review. Surg Oncol 2021; 37:101524. [PMID: 33556883 DOI: 10.1016/j.suronc.2021.101524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/07/2021] [Accepted: 01/25/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND OBJECTIVES Colorectal cancer is still one of the leading causes of cancer-related deaths worldwide and specific tools to improve disease assessment and treatment response are advocated. The aim of this study was to analyze miRNAs expression in metastatic and non-metastatic colorectal cancer, in order to identify reliable biomarkers suitable for prognosis, treatment and patient's monitoring. MATERIAL AND METHODS Among 25 patients (mean age 71 ± 12 years; Female/Male: 12/13) submitted to laparoscopic colorectal resection between August 2017 and February 2019, miRNAs were extracted from fresh frozen tissues of solid tumors. Gene expression's analysis arising from microarray technology was performed. RESULTS Pathological evaluation identified 15 metastatic patients (8 presenting with stage III and 7 with stage IV cancers) and 10 non-metastatic patients (4 presenting with stage I and 6 stage II cancers). Bioinformatic analysis of solid biopsies revealed 16 miRNAs (11 upregulated and 5 downregulated) differently expressed between metastatic and non-metastatic groups, with three miRNAs (miR-7515, miR-7109-5p and miR-6831-5p) never linked to colorectal cancer before. CONCLUSIONS Our study showed an association between miRNAs and metastatic colorectal cancer, suggesting their potential role as biomarkers for tumor management, if confirmed by further studies.
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Affiliation(s)
- Elisa Francone
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
| | - Sergio Gentilli
- Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy
| | - Gregorio Santori
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Cesare Stabilini
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Rosario Fornaro
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
| | - Marco Frascio
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
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Salmond N, Williams KC. Isolation and characterization of extracellular vesicles for clinical applications in cancer - time for standardization? NANOSCALE ADVANCES 2021; 3:1830-1852. [PMID: 36133088 PMCID: PMC9419267 DOI: 10.1039/d0na00676a] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 02/13/2021] [Indexed: 05/08/2023]
Abstract
Extracellular vesicles (EVs) are nanometer sized lipid enclosed particles released by all cell types into the extracellular space and biological fluids in vivo, and into cell culture media in vitro. An important physiological role of EVs is cell-cell communication. EVs interact with, and deliver, their contents to recipient cells in a functional capacity; this makes EVs desirable vehicles for the delivery of therapeutic cargoes. In addition, as EVs contain proteins, lipids, glycans, and nucleic acids that reflect their cell of origin, their potential utility in disease diagnosis and prognostication is of great interest. The number of published studies analyzing EVs and their contents in the pre-clinical and clinical setting is rapidly expanding. However, there is little standardization as to what techniques should be used to isolate, purify and characterize EVs. Here we provide a comprehensive literature review encompassing the use of EVs as diagnostic and prognostic biomarkers in cancer. We also detail their use as therapeutic delivery vehicles to treat cancer in pre-clinical and clinical settings and assess the EV isolation and characterization strategies currently being employed. Our report details diverse isolation strategies which are often dependent upon multiple factors such as biofluid type, sample volume, and desired purity of EVs. As isolation strategies vary greatly between studies, thorough EV characterization would be of great importance. However, to date, EV characterization in pre-clinical and clinical studies is not consistently or routinely adhered to. Standardization of EV characterization so that all studies image EVs, quantitate protein concentration, identify the presence of EV protein markers and contaminants, and measure EV particle size and concentration is suggested. Additionally, the use of RNase, DNase and protease EV membrane protection control experiments is recommended to ensure that the cargo being investigated is truly EV associated. Overall, diverse methodology for EV isolation is advantageous as it can support different sample types and volumes. Nevertheless, EV characterization is crucial and should be performed in a rigorous manor.
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Affiliation(s)
- Nikki Salmond
- University of British Columbia, Faculty of Pharmaceutical Sciences Vancouver V6T 1Z3 Canada
| | - Karla C Williams
- University of British Columbia, Faculty of Pharmaceutical Sciences Vancouver V6T 1Z3 Canada
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Yu M, Song XG, Zhao YJ, Dong XH, Niu LM, Zhang ZJ, Shang XL, Tang YY, Song XR, Xie L. Circulating Serum Exosomal Long Non-Coding RNAs FOXD2-AS1, NRIR, and XLOC_009459 as Diagnostic Biomarkers for Colorectal Cancer. Front Oncol 2021; 11:618967. [PMID: 33777763 PMCID: PMC7996089 DOI: 10.3389/fonc.2021.618967] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/05/2021] [Indexed: 12/15/2022] Open
Abstract
Background Exosomes derived from cancer cells encapsulate various kinds of tumor-specific molecules and thus can interact with adjacent or distant cells to mediate information exchange. Long non-coding RNAs (lncRNAs) in exosomes have the potential as diagnostic and prognostic biomarkers in different types of cancers. The current study was aimed to identify circulating exosomal lncRNAs for the diagnosis of colorectal cancer (CRC). Methods Exosomes were isolated from the serum by ultracentrifugation and verified by transmission electron microscope (TEM), qNano, and immunoblotting. Exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 were selected by lncRNA microarray and validated by qPCR in 203 CRC patients and 201 healthy donors. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficiency of serum exosomal lncRNAs. Results Exosomal FOXD2-AS1, NRIR, and XLOC_009459 (TCONS_00020073) levels were significantly upregulated in 203 CRC patients and 80 early-stage CRC patients compared to 201 healthy donors, possessing the area under the curve (AUC) of 0.728, 0.660, and 0.682 for CRC, as well as 0.743, 0.660, and 0.689 for early-stage CRC, respectively. Notably, their combination demonstrated the markedly elevated AUC of 0.736 for CRC and 0.758 for early-stage CRC, indicating their potential as diagnostic biomarkers for CRC. Conclusions Our data suggested that exosomal lncRNAs FOXD2-AS1, NRIR, and XLOC_009459 act as the promising biomarkers for the diagnostics of CRC and early-stage CRC.
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Affiliation(s)
- Miao Yu
- Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.,Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Department of Clinical Laboratory, Jinan Qilu Medical Inspection Co., Ltd., Jinan, China
| | - Xing-Guo Song
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Ya-Jing Zhao
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xiao-Han Dong
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Li-Min Niu
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Zhi-Jun Zhang
- Department of Clinical Laboratory, Tai'an City Central Hospital, Tai'an, China
| | - Xiao-Ling Shang
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - You-Yong Tang
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xian-Rang Song
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Li Xie
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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Xu Y, Chen X, Zhao C, Wang X, Cheng Y, Xi F, Yao X, Zhang L, Yang G, Yu T. MiR-99b-5p Attenuates Adipogenesis by Targeting SCD1 and Lpin1 in 3T3-L1 Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:2564-2575. [PMID: 33599498 DOI: 10.1021/acs.jafc.0c07451] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
The number and distribution of adipocytes directly affect the quality of livestock meat products. The analysis of the adipogenesis mechanism is the basis for improving meat quality. The formation of adipocytes is regulated by many factors, including a class of endogenous small RNAs, named microRNA (miRNA). Previous studies have shown that miRNAs could affect adipogenesis by post-transcriptional regulation of target genes. In our study, a decreased miR-99b-5p expression level was found in the adipose tissue of obese mice. Overexpression of miR-99b-5p could increase cell proliferation by promoting the cell cycle while inhibiting cell differentiation. In addition, interference with miR-99b-5p obtained the opposite result. Furthermore, the proteomics sequencing analysis screened 1154 differentially expressed proteins, which are closely related to adipocyte differentiation and fatty acid metabolism. In addition, the results of the dual-luciferase test showed that miR-99b-5p can directly target the proteins SCD1 and Lpin1 with significantly different expression levels in proteomic sequencing. Then, this result was verified at the level of mRNA and protein in a further study. Collectively, these results suggested that miR-99b-5p may be a target for improving meat quality.
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Affiliation(s)
- Yanting Xu
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Xiaochang Chen
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Chen Zhao
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Xiaoting Wang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Ye Cheng
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Fengxue Xi
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Xiangping Yao
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Lei Zhang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Gongshe Yang
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
| | - Taiyong Yu
- Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling Shanxi 712100, China
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Diaz-Garrido N, Cordero C, Olivo-Martinez Y, Badia J, Baldomà L. Cell-to-Cell Communication by Host-Released Extracellular Vesicles in the Gut: Implications in Health and Disease. Int J Mol Sci 2021; 22:ijms22042213. [PMID: 33672304 PMCID: PMC7927122 DOI: 10.3390/ijms22042213] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/17/2021] [Accepted: 02/19/2021] [Indexed: 12/12/2022] Open
Abstract
Communication between cells is crucial to preserve body homeostasis and health. Tightly controlled intercellular dialog is particularly relevant in the gut, where cells of the intestinal mucosa are constantly exposed to millions of microbes that have great impact on intestinal homeostasis by controlling barrier and immune functions. Recent knowledge involves extracellular vesicles (EVs) as mediators of such communication by transferring messenger bioactive molecules including proteins, lipids, and miRNAs between cells and tissues. The specific functions of EVs principally depend on the internal cargo, which upon delivery to target cells trigger signal events that modulate cellular functions. The vesicular cargo is greatly influenced by genetic, pathological, and environmental factors. This finding provides the basis for investigating potential clinical applications of EVs as therapeutic targets or diagnostic biomarkers. Here, we review current knowledge on the biogenesis and cargo composition of EVs in general terms. We then focus the attention to EVs released by cells of the intestinal mucosa and their impact on intestinal homeostasis in health and disease. We specifically highlight their role on epithelial barrier integrity, wound healing of epithelial cells, immunity, and microbiota shaping. Microbiota-derived EVs are not reviewed here.
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Affiliation(s)
- Natalia Diaz-Garrido
- Secció de Bioquímica i Biología Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; (N.D.-G.); (C.C.); (Y.O.-M.); (J.B.)
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain
| | - Cecilia Cordero
- Secció de Bioquímica i Biología Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; (N.D.-G.); (C.C.); (Y.O.-M.); (J.B.)
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain
| | - Yenifer Olivo-Martinez
- Secció de Bioquímica i Biología Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; (N.D.-G.); (C.C.); (Y.O.-M.); (J.B.)
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain
| | - Josefa Badia
- Secció de Bioquímica i Biología Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; (N.D.-G.); (C.C.); (Y.O.-M.); (J.B.)
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain
| | - Laura Baldomà
- Secció de Bioquímica i Biología Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; (N.D.-G.); (C.C.); (Y.O.-M.); (J.B.)
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain
- Correspondence: ; Tel.: +34-93-403-44-96
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Four circulating exosomal miRNAs as novel potential biomarkers for the early diagnosis of human colorectal cancer. Tissue Cell 2021; 70:101499. [PMID: 33550035 DOI: 10.1016/j.tice.2021.101499] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 01/17/2021] [Accepted: 01/19/2021] [Indexed: 02/08/2023]
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Our study aimed to identify novel circulating miRNAs as early diagnostic biomarkers of CRC. The Gene Expression Omnibus (GEO) datasets were analyzed by using the online tool GEO2R. Isolated exosomes were verified by using the transmission electron microscope (TEM), Nanosight, and western blot. qRT-PCR was implemented to examine miRNA expression. The diagnostic value of circulating exosomal miRNAs was identified by using the receiver operating characteristic curve (ROC). In this study, we found that serum exosomal miRNAs are more suitable for diagnosing CRC when compared to serum miRNAs. Furthermore, we identified four exosomal miRNAs (miR-126, miR-1290, miR-23a, and miR-940) in the serum of CRC patients as novel potential biomarkers for the early diagnosis of CRC because they showed high diagnostic values to differentiate CRC patients at TNM stage I from healthy controls (HCs). In addition, our data suggested that CRC cells may secrete miRNAs into the extracellular environment through exosomes regardless of intracellular miRNA expression. In conclusion, we identified serum exosomal miR-126, miR-1290, miR-23a, and miR-940 as novel potential biomarkers for the early diagnosis of CRC.
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