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Golestannejad P, Monkaresi M, Zhian Zargaran F, Khosravani M, Asgari P, Mobaraki H, Gorjizad M, Hasany S, Senobari Ghezeljehmeidan A, Hemmati S, Zand S, Ghasemi P, Asadi Anar M. Role of Cancer Associated Fibroblast (CAF) derived miRNAs on head and neck malignancies microenvironment: a systematic review. BMC Cancer 2025; 25:582. [PMID: 40169971 PMCID: PMC11960023 DOI: 10.1186/s12885-025-13965-9] [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: 07/23/2024] [Accepted: 03/18/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND AND AIM MicroRNAs (miRNAs) play a key role in regulating gene expression within the tumor microenvironment, influencing cancer progression and therapy response. Cancer-associated fibroblasts (CAFs) contribute to tumor development by secreting exosomal miRNAs that promote proliferation, invasion, and resistance. This systematic review evaluates the impact of CAF-derived miRNAs on head and neck malignancies. METHODS A systematic search was conducted in PubMed, Scopus, WOS, and Google Scholar following PRISMA guidelines. Studies focusing on CAF-derived miRNAs in head and neck cancers were included. Data extraction covered study characteristics, miRNA profiling methods, functional roles, and clinical significance. The Scirap tool was used for quality assessment. RESULTS Among 921 identified articles, 21 met the inclusion criteria. Findings indicate that miR-21-5p, miR-106-5p, and miR-196a drive tumor progression in oral squamous cell carcinoma (OSCC), while miR-124 and miR-34a-5p act as suppressors. In esophageal squamous cell carcinoma (ESCC), miR-21 and miR-27a/b contribute to chemotherapy resistance, whereas miR-100-5p inhibits lymphangiogenesis. In head and neck squamous cell carcinoma (HNSCC), miR-196a and miR-196b may serve as diagnostic biomarkers. Exosomal miR-106a-5p promotes nasopharyngeal carcinoma (NPC) metastasis, and miR-7 and miR-196a contribute to therapy resistance in head and neck cancer (HNC). CONCLUSION CAF-derived miRNAs significantly influence tumor progression, metastasis, and therapy resistance. These findings highlight their potential as biomarkers and therapeutic targets, warranting further clinical research for personalized treatment strategies.
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Affiliation(s)
- Parsa Golestannejad
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mohamadparsa Monkaresi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - Mohammad Khosravani
- Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Pouya Asgari
- Ahvaz Jondishapur University of Medical Sciences, Ahvaz, Iran
| | - Hesam Mobaraki
- Faculty of Medicine, İStanbul Yeniyuzyil University, Istanbul, Turkey
| | - Mansour Gorjizad
- School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saina Hasany
- Islamic Azad University Tehran Medical Sciences, Tehran, Iran
| | | | - Sara Hemmati
- Gulian University of Medical Sciences, Rasht, Iran
| | - Samaneh Zand
- Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Parsa Ghasemi
- School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mahsa Asadi Anar
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Arabi Ave, Daneshjoo Blvd, Velenjak, Tehran, 19839-63113, Iran.
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Alizadeh M, Ghasemi H, Bazhan D, Mohammadi Bolbanabad N, Rahdan F, Arianfar N, Vahedi F, Khatami SH, Taheri-Anganeh M, Aiiashi S, Armand N. MicroRNAs in disease States. Clin Chim Acta 2025; 569:120187. [PMID: 39938625 DOI: 10.1016/j.cca.2025.120187] [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: 11/24/2024] [Revised: 02/08/2025] [Accepted: 02/08/2025] [Indexed: 02/14/2025]
Abstract
This review highlights the role of miRNAs in various diseases affecting major organ systems. miRNAs are small, non-coding RNA molecules that regulate numerous genes. Dysregulation of miRNAs is linked to many pathological conditions due to their involvement in gene silencing and cellular pathways. We discuss miRNA expression patterns, their physiological and pathological roles, and how changes in miRNA levels contribute to disease. Notably, miRNAs like miR-499 and miR-21 are implicated in heart failure and atherosclerosis. miRNA dysregulation is also associated with colorectal and gastric cancers, influencing tumorigenesis and chemoresistance. In neurological diseases, miRNAs exhibit diverse profiles that affect neurodevelopment and degeneration. Additionally, miRNAs modulate cell function in reproductive organs, impacting fertility and cancer progression. miRNAs such as miR-192 and miR-204 serve as biomarkers for nephropathy and acute kidney injury. These miRNAs are involved in skeletal muscle diseases, contributing to conditions like osteoporosis and sarcopenia. miRNAs function as oncogenes or tumor suppressors in cancer, highlighting their potential in diagnostics and therapy. Further research is needed to develop miRNA-based diagnostics and treatments.
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Affiliation(s)
- Mehdi Alizadeh
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Ghasemi
- Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran
| | - Donya Bazhan
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Fereshteh Rahdan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Narges Arianfar
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzaneh Vahedi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | - Saleh Aiiashi
- Abadan University of Medical Sciences, Abadan, Iran.
| | - Nezam Armand
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.
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Na H, Koo BI, Park JC, Lim J, Kim Y, Chung HJ, Nam YS. Live-Cell Imaging of MicroRNA Expression via Photoinduced Electron Transfer Controlled by Catalytic Hairpin Assembly. Adv Healthc Mater 2024; 13:e2401483. [PMID: 38889395 DOI: 10.1002/adhm.202401483] [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: 04/22/2024] [Revised: 06/14/2024] [Indexed: 06/20/2024]
Abstract
MicroRNAs (miRNAs) serve as emerging biomarkers for a range of diseases, and their quantitative analysis draws increasing attention. Yet, current invasive methods limit continuous tracking within living cells. To overcome this, a nonenzymatic DNA-based nanoprobe is developed for dynamic, noninvasive miRNA tracking via live-cell imaging. This probe features a unique hairpin DNA structure with five guanines that act as internal quenchers, suppressing fluorescence from an attached fluorophore via photoinduced electron transfer. Target miRNA initiates toehold-mediated strand displacement, restoring, and amplifying the fluorescence signal. Additionally, by introducing a single mismatch to the hairpin DNA, the nanoprobe's sensitivity is significantly enhanced, lowering the detection limit to about 60 pM without compromising specificity. To optimize intracellular delivery for prolonged monitoring, the nanoprobe is encapsulated within multilamellar lipid nanovesicles, fluorescently labeled for dual-wavelength ratiometric analysis. The proposed nanoprobe demonstrates a significant advance in live-cell miRNA detection, promising enhanced in situ analysis for a better understanding of miRNAs' pathophysiological function.
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Affiliation(s)
- Hyebin Na
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Bon Il Koo
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Jae Chul Park
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Jiwoo Lim
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Yoosik Kim
- Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Hyun Jung Chung
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Yoon Sung Nam
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
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4
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Küçük C, Esmeray Sönmez E, Hatipoğlu T, Yuan H, Hu X, Ceylan A, Siviş ZÖ, Demirağ B, Ataseven E, İnce D, Altun Z, Aktaş S, Özsan N, Erdağ TK, Ayhan YS, Demir Gündoğan B, Çetingül N, Özer E, Kutluk T, Olgun N. Potential diagnostic and prognostic biomarkers of pediatric Burkitt lymphoma identified through miRNA expression profiling. Pediatr Res 2024:10.1038/s41390-024-03478-9. [PMID: 39261659 DOI: 10.1038/s41390-024-03478-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 07/16/2024] [Accepted: 08/01/2024] [Indexed: 09/13/2024]
Abstract
BACKGROUND Pediatric Burkitt lymphoma (pBL) is the most common non-Hodgkin lymphoma in children. These patients require prompt diagnosis and initiation of therapy due to rapid tumor growth. The roles of tumor tissue and circulating microRNAs (miRNAs) in the diagnosis or prognostication have not been fully elucidated in pBLs. METHODS Differentially expressed (DE) miRNAs were identified with microRNA sequencing (miRNA-Seq) in tumor tissues and plasma of diagnostic pBLs. The diagnostic potential of total miRNA concentrations and overexpressed miRNAs were evaluated through receiver operating characteristic (ROC) analyses. Log-rank test was employed to evaluate survival differences associated with DE miRNAs. Selected miRNA expressions were cross-validated with quantitative reverse transcription PCR (qRT-PCR). RESULTS Total circulating cell-free miRNAs were higher in pBL cases compared to controls. Cancer-associated pathways were enriched among miRNAs differentially expressed in pBL tumor tissues. Several upregulated miRNAs in pBL tumors demonstrated high diagnostic potential. Similarly, ROC analysis of overexpressed plasma miRNAs revealed circulating cell-free or exosomal miRNAs that can distinguish pBLs from control cases. Indeed, integrative analysis of overexpressed circulating exosomal miRNAs showed an enhanced diagnostic potential for certain triple combinations. Kaplan-Meier analyses of DE miRNAs in tumor tissues identified miRNAs predicting overall survival. CONCLUSIONS Differentially expressed miRNAs in tumor tissue and plasma of pBL have the potential to improve diagnosis and prognosis. IMPACT Differentially expressed miRNAs in treatment-naive pediatric Burkitt lymphoma cases have diagnostic or prognostic biomarker potential. This is the first study that applied miRNA-Seq on treatment-naive pediatric Burkitt lymphoma cases for identification of differentially expressed miRNAs both in tumor tissue and plasma samples with diagnostic potential. Through systematic analysis of differentially expressed miRNAs, tumor tissue miRNAs associated with the overall survival of pBLs have been discovered. The clinically significant, differentially expressed miRNAs identified in pediatric Burkitt lymphoma cases can potentially improve the current tissue-based or non-invasive clinical practice in terms of diagnosis or prognostication.
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Affiliation(s)
- Can Küçük
- Department of Medical Biology, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye.
- İzmir Biomedicine and Genome Center, İzmir, Türkiye.
| | - Esra Esmeray Sönmez
- İzmir Biomedicine and Genome Center, İzmir, Türkiye
- İzmir International Biomedicine and Genome Institute, Dokuz Eylül University, İzmir, Türkiye
| | - Tevfik Hatipoğlu
- İzmir Biomedicine and Genome Center, İzmir, Türkiye
- İzmir International Biomedicine and Genome Institute, Dokuz Eylül University, İzmir, Türkiye
| | - Hongling Yuan
- Department of Basic Oncology, Oncology Institute, Dokuz Eylül University, İzmir, Türkiye
| | - Xiaozhou Hu
- Department of Medical Biochemistry, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye
| | - Arda Ceylan
- İzmir Biomedicine and Genome Center, İzmir, Türkiye
- İzmir International Biomedicine and Genome Institute, Dokuz Eylül University, İzmir, Türkiye
| | - Zuhal Önder Siviş
- İzmir Tepecik Education and Research Hospital, Health Sciences University, İzmir, Türkiye
| | - Bengü Demirağ
- Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, Health Sciences University, İzmir, Türkiye
| | - Eda Ataseven
- Department of Child Health and Diseases, Faculty of Medicine, Ege University, İzmir, Türkiye
| | - Dilek İnce
- Department of Clinical Oncology, Oncology Institute, Dokuz Eylül University, İzmir, Türkiye
| | - Zekiye Altun
- Department of Basic Oncology, Oncology Institute, Dokuz Eylül University, İzmir, Türkiye
| | - Safiye Aktaş
- Department of Basic Oncology, Oncology Institute, Dokuz Eylül University, İzmir, Türkiye
| | - Nazan Özsan
- Department of Medical Pathology, Ege University, İzmir, Türkiye
| | - Taner Kemal Erdağ
- Department of Otorhinolaryngology, Dokuz Eylül University School of Medicine, İzmir, Türkiye
| | - Yavuz Selim Ayhan
- Department of Child Health and Diseases, Faculty of Medicine, Mersin University, Mersin, Türkiye
| | - Begümhan Demir Gündoğan
- Department of Child Hematology and Oncology, Faculty of Medicine, Mersin University, Mersin, Türkiye
| | - Nazan Çetingül
- Department of Child Health and Diseases, Faculty of Medicine, Ege University, İzmir, Türkiye
| | - Erdener Özer
- Department of Medical Pathology, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye
| | - Tezer Kutluk
- Department of Pediatric Oncology, Faculty of Medicine and Cancer Institute, Hacettepe University, Ankara, Türkiye
| | - Nur Olgun
- Department of Pediatric Oncology, Oncology Institute, Dokuz Eylül University, İzmir, Türkiye
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5
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Azam HMH, Rößling RI, Geithe C, Khan MM, Dinter F, Hanack K, Prüß H, Husse B, Roggenbuck D, Schierack P, Rödiger S. MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review. Front Mol Neurosci 2024; 17:1386735. [PMID: 38883980 PMCID: PMC11177777 DOI: 10.3389/fnmol.2024.1386735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/12/2024] [Indexed: 06/18/2024] Open
Abstract
Neurodegenerative diseases (NDs) are characterized by abnormalities within neurons of the brain or spinal cord that gradually lose function, eventually leading to cell death. Upon examination of affected tissue, pathological changes reveal a loss of synapses, misfolded proteins, and activation of immune cells-all indicative of disease progression-before severe clinical symptoms become apparent. Early detection of NDs is crucial for potentially administering targeted medications that may delay disease advancement. Given their complex pathophysiological features and diverse clinical symptoms, there is a pressing need for sensitive and effective diagnostic methods for NDs. Biomarkers such as microRNAs (miRNAs) have been identified as potential tools for detecting these diseases. We explore the pivotal role of miRNAs in the context of NDs, focusing on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease, and Amyotrophic Lateral Sclerosis. The review delves into the intricate relationship between aging and NDs, highlighting structural and functional alterations in the aging brain and their implications for disease development. It elucidates how miRNAs and RNA-binding proteins are implicated in the pathogenesis of NDs and underscores the importance of investigating their expression and function in aging. Significantly, miRNAs exert substantial influence on post-translational modifications (PTMs), impacting not just the nervous system but a wide array of tissues and cell types as well. Specific miRNAs have been found to target proteins involved in ubiquitination or de-ubiquitination processes, which play a significant role in regulating protein function and stability. We discuss the link between miRNA, PTM, and NDs. Additionally, the review discusses the significance of miRNAs as biomarkers for early disease detection, offering insights into diagnostic strategies.
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Affiliation(s)
- Hafiz Muhammad Husnain Azam
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
| | - Rosa Ilse Rößling
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
- Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Christiane Geithe
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
- Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, The Brandenburg Medical School Theodor Fontane and the University of Potsdam, Berlin, Germany
| | - Muhammad Moman Khan
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
| | - Franziska Dinter
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
- PolyAn GmbH, Berlin, Germany
| | - Katja Hanack
- Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany
| | - Harald Prüß
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
- Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Britta Husse
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
| | - Dirk Roggenbuck
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
| | - Peter Schierack
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
| | - Stefan Rödiger
- Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany
- Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, The Brandenburg Medical School Theodor Fontane and the University of Potsdam, Berlin, Germany
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Fan C, Xie L, Zhao F, Wang J, Lin X, Chen X. Novel fluorescence nano-orbital biosensor for highly sensitive microRNA detection. Anal Chim Acta 2024; 1288:342172. [PMID: 38220303 DOI: 10.1016/j.aca.2023.342172] [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: 09/07/2023] [Revised: 11/18/2023] [Accepted: 12/20/2023] [Indexed: 01/16/2024]
Abstract
BACKGROUND MicroRNAs play an important role in regulating cell function and gene expression. Early prevention and clinical diagnosis of diseases have high requirements for high-sensitivity detection of microRNAs. Due to the limitations of tedious operation and large sample size, miRNA with small molecular weight and low expression abundance cannot be accurately detected in traditional miRNA detection. To improve the sensitivity and accuracy of detection, we established a novel biosensor based on nucleic acid circuit of signal amplification, which converted miRNA recognition into a fluorescence signal for amplification. RESULTS We designed a biosensor based on an exponential amplification reaction with cascaded HCR and DNAzyme nucleic acid circuit (named E-NOF biosensor) by amplicon sub-fragments to trigger the construction of fluorescence nano-orbitals (NOF), which could be used to detect miRNA ultrasensitively. By modifying two fluorophores (Cy3 and Cy5) on the chain of constructing nano-orbitals, when the amplicon triggered the construction of nano-orbitals, fluorescence resonance energy transfer (FRET) occurred between Cy3 and Cy5, and then two fluorescence signals with different trends could be observed. Therefore, through the ratio of the two signals, we could quantitatively and quickly detect the miRNA from 1 fM to 100 nM, and the E-NOF biosensor detection limit was as low as 0.129 fM. Furthermore, the HCR nucleic acid circuit cascaded with DNAzyme could enrich the fluorophores on the nano-orbitals and significantly enhance the fluorescence signal by accelerating the reaction rate. SIGNIFICANCE According to our understanding, the E-NOF biosensor is the first strategy to cascade EXPAR with HCR and DNAzyme nucleic acid circuit for miRNA-1246 detection. Accurate results can be obtained in only 120 min. Compared with the traditional HCR system, the sensitivity of the new E-NOF biosensor is increased by 1 × 109 times. Furthermore, the biosensor can also detect biomarkers in human serum samples. It has great potential in miRNA detection and identification.
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Affiliation(s)
- Cong Fan
- College of Chemistry, Fuzhou University, 2 Xueyuan Road, Fuzhou, 350116, China
| | - Longjie Xie
- College of Chemistry, Fuzhou University, 2 Xueyuan Road, Fuzhou, 350116, China
| | - Feng Zhao
- College of Chemistry, Fuzhou University, 2 Xueyuan Road, Fuzhou, 350116, China; Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
| | - Jingjing Wang
- College of Chemistry, Fuzhou University, 2 Xueyuan Road, Fuzhou, 350116, China
| | - Xiandong Lin
- Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
| | - Xian Chen
- College of Chemistry, Fuzhou University, 2 Xueyuan Road, Fuzhou, 350116, China.
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Liao Q, Fu X, Zhuo L, Chen H. An efficient model for predicting human diseases through miRNA based on multiple-types of contrastive learning. Front Microbiol 2023; 14:1325001. [PMID: 38163075 PMCID: PMC10755968 DOI: 10.3389/fmicb.2023.1325001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 11/16/2023] [Indexed: 01/03/2024] Open
Abstract
Multiple studies have demonstrated that microRNA (miRNA) can be deeply involved in the regulatory mechanism of human microbiota, thereby inducing disease. Developing effective methods to infer potential associations between microRNAs (miRNAs) and diseases can aid early diagnosis and treatment. Recent methods utilize machine learning or deep learning to predict miRNA-disease associations (MDAs), achieving state-of-the-art performance. However, the problem of sparse neighborhoods of nodes due to lack of data has not been well solved. To this end, we propose a new model named MTCL-MDA, which integrates multiple-types of contrastive learning strategies into a graph collaborative filtering model to predict potential MDAs. The model adopts a contrastive learning strategy based on topology, which alleviates the damage to model performance caused by sparse neighborhoods. In addition, the model also adopts a semantic-based contrastive learning strategy, which not only reduces the impact of noise introduced by topology-based contrastive learning, but also enhances the semantic information of nodes. Experimental results show that our model outperforms existing models on all evaluation metrics. Case analysis shows that our model can more accurately identify potential MDA, which is of great significance for the screening and diagnosis of real-life diseases. Our data and code are publicly available at: https://github.com/Lqingquan/MTCL-MDA.
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Affiliation(s)
- Qingquan Liao
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Xiangzheng Fu
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Linlin Zhuo
- School of Data Science and Artificial Intelligence, Wenzhou University of Technology, Wenzhou, China
| | - Hao Chen
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
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8
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Frydrychowicz M, Kuszel Ł, Dworacki G, Budna-Tukan J. MicroRNA in lung cancer-a novel potential way for early diagnosis and therapy. J Appl Genet 2023; 64:459-477. [PMID: 36821071 PMCID: PMC10457410 DOI: 10.1007/s13353-023-00750-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/31/2023] [Accepted: 02/07/2023] [Indexed: 02/24/2023]
Abstract
Lung cancer is the most common cause of cancer-related deaths in the world. One of the reasons of poor prognosis and high mortality of lung cancer patients is the diagnosis of the disease in its advanced stage. Despite innovative diagnostic methods and multiple completed and ongoing clinical trials aiming at therapy improvement, no significant increase in patients' long-term survival has been noted over last decades. Patients would certainly benefit from early detection of lung cancer. Therefore, it is crucial to find new biomarkers that can help predict outcomes and tumor responses in order to maximize therapy effectiveness and avoid over- or under-treating patients with lung cancer. Nowadays, scientists' attention is mainly dedicated to so-called liquid biopsy, which is fully non-invasive and easily available method based on simple blood draw. Among common liquid biopsy elements, circulating tumor nucleic acids are worth mentioning. Epigenetic biomarkers, particularly miRNA expression, have several distinct features that make them promising prognostic markers. In this review, we described miRNA's involvement in tumorigenesis and present it as a predictor of cancer development and progression, potential indicator of treatment efficacy, and most importantly promising therapeutic target.
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Affiliation(s)
- Magdalena Frydrychowicz
- Department of Clinical Immunology, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Łukasz Kuszel
- Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Grzegorz Dworacki
- Department of Clinical Immunology, Poznan University of Medical Sciences, 60-806 Poznan, Poland
| | - Joanna Budna-Tukan
- Department of Histology and Embryology, Poznan University of Medical Sciences, 61-781 Poznan, Poland
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9
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Al Hrout A, Levesque MP, Chahwan R. Investigating the tumor-immune microenvironment through extracellular vesicles from frozen patient biopsies and 3D cultures. Front Immunol 2023; 14:1176175. [PMID: 37304281 PMCID: PMC10248017 DOI: 10.3389/fimmu.2023.1176175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 05/04/2023] [Indexed: 06/13/2023] Open
Abstract
Melanomas are highly immunogenic tumors that have been shown to activate the immune response. Nonetheless, a significant portion of melanoma cases are either unresponsive to immunotherapy or relapsed due to acquired resistance. During melanomagenesis, melanoma and immune cells undergo immunomodulatory mechanisms that aid in immune resistance and evasion. The crosstalk within melanoma microenvironment is facilitated through the secretion of soluble factors, growth factors, cytokines, and chemokines. In addition, the release and uptake of secretory vesicles known as extracellular vesicles (EVs) play a key role in shaping the tumor microenvironment (TME). Melanoma-derived EVs have been implicated in immune suppression and escape, promoting tumor progression. In the context of cancer patients, EVs are usually isolated from biofluids such as serum, urine, and saliva. Nonetheless, this approach neglects the fact that biofluid-derived EVs reflect not only the tumor, but also include contributions from different organs and cell types. For that, isolating EVs from tissue samples allows for studying different cell populations resident at the tumor site, such as tumor-infiltrating lymphocytes and their secreted EVs, which play a central anti-tumor role. Herein, we outline the first instance of a method for EV isolation from frozen tissue samples at high purity and sensitivity that can be easily reproduced without the need for complicated isolation methods. Our method of processing the tissue not only circumvents the need for hard-to-acquire freshly isolated tissue samples, but also preserves EV surface proteins which allows for multiplex surface markers profiling. Tissue-derived EVs provide insight into the physiological role of EVs enrichment at tumor sites, which can be overlooked when studying circulating EVs coming from different sources. Tissue-derived EVs could be further characterized in terms of their genomics and proteomics to identify possible mechanisms for regulating the TME. Additionally, identified markers could be correlated to overall patient survival and disease progression for prognostic purposes.
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Affiliation(s)
- Ala’a Al Hrout
- Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
| | - Mitchell P. Levesque
- Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Richard Chahwan
- Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
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10
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Galindo Torres BP, García Girón C, Alcaraz Ortega R, Saiz López P, Adiego Leza MI, Grijalba Uche MV. Knowledge and expectations about miRNAs as biomarkers in head and neck squamous cell cancers. Am J Otolaryngol 2023; 44:103771. [PMID: 36603378 DOI: 10.1016/j.amjoto.2022.103771] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 12/18/2022] [Indexed: 12/31/2022]
Abstract
Head and neck squamous cell cancer patients suffer from a high postoperative recurrence rate and poor prognosis. Thus, it is essential to better understand the underlying molecular mechanisms and identify the role of new biomarkers. Recent research has shown that the dysregulation of microRNAs is a potential biomarker as a screening or prognostic tool. Moreover, the literature reveals its promising usefulness to select the best treatment strategy and monitor tumour response. The purpose of this review is to identify and synthesize the available literature on microRNAs as biomarkers that could help manage patients with head and neck squamous cell cancer. A search in scientific databases was completed, including all relevant articles related to circulating microRNAs in head and neck squamous cell cancer published in English or Spanish. We focused on articles whose main findings were related to their usefulness in diagnosis and prognosis. Conclusion: Knowledge of microRNAs opens the possibilities that these molecules offer in terms of monitoring cancer disease in a less-invasive, simple manner, allowing for serial sampling to assess the response to treatment and minimal residual disease. It is yet to be determined whether liquid biopsy will replace the traditional biopsy in the future but it represents a change in the paradigm of management of head and neck squamous cell cancer.
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Affiliation(s)
| | | | | | - Patricia Saiz López
- Pathological Anatomy Department, Universitary Hospital of Burgos, Burgos, Spain
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11
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Kaur A, Mahmoud R, Megalathan A, Pettit S, Dhakal S. Multiplexed smFRET Nucleic Acid Sensing Using DNA Nanotweezers. BIOSENSORS 2023; 13:119. [PMID: 36671954 PMCID: PMC9856376 DOI: 10.3390/bios13010119] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/01/2023] [Accepted: 01/03/2023] [Indexed: 06/17/2023]
Abstract
The multiplexed detection of disease biomarkers is part of an ongoing effort toward improving the quality of diagnostic testing, reducing the cost of analysis, and accelerating the treatment processes. Although significant efforts have been made to develop more sensitive and rapid multiplexed screening methods, such as microarrays and electrochemical sensors, their limitations include their intricate sensing designs and semi-quantitative detection capabilities. Alternatively, fluorescence resonance energy transfer (FRET)-based single-molecule counting offers great potential for both the sensitive and quantitative detection of various biomarkers. However, current FRET-based multiplexed sensing typically requires the use of multiple excitation sources and/or FRET pairs, which complicates labeling schemes and the post-analysis of data. We present a nanotweezer (NT)-based sensing strategy that employs a single FRET pair and is capable of detecting multiple targets. Using DNA mimics of miRNA biomarkers specific to triple-negative breast cancer (TNBC), we demonstrated that the developed sensors are sensitive down to the low picomolar range (≤10 pM) and can discriminate between targets with a single-base mismatch. These simple hybridization-based sensors hold great promise for the sensitive detection of a wider spectrum of nucleic acid biomarkers.
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12
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Treerattrakoon K, Roeksrungruang P, Dharakul T, Japrung D, Faulds K, Graham D, Bamrungsap S. Detection of a miRNA biomarker for cancer diagnosis using SERS tags and magnetic separation. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2022; 14:1938-1945. [PMID: 35441184 DOI: 10.1039/d2ay00210h] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Detection of miR-29a, a biomarker of cancers, using SERS tags and magnetic separation is described. The assay was designed to detect the miR-29a sequence by taking the complementary sequence and splitting it into a capture and detection probe. The SERS tags comprised the highly Raman active molecule 4-mercaptobenzoic acid (4-MBA) and DNA detection probes assembled onto the surface of gold nanorods (AuNRs) through the self-assembly process. The capture DNA conjugated magnetic nanoparticles (MNPs) were applied as capture probes. The detection was based on the hybridisation and sandwich complex formation. The resultant hybridisation-dependent complexes were recovered and enriched from the samples by magnetic separation. The enriched solution containing target miRNA hybridised with capture probes were dropped on a foil-covered slide to form a droplet for SERS analysis. A characteristic spectrum of 4-MBA was observed to indicate the presence of the miR-29a in the samples. The sensitivity of the assay is examined by measuring the SERS signal of the samples containing different concentrations of the miR-29a. The SERS intensity appears to increase with the concentration of miR-29a. The limit of detection (LOD) was found to be 10 pM without any amplification process. In addition, the selectivity and feasibility of the assay in complex media are evaluated with the non-target miRNAs comprising different sequences from the target miR-29a. The system was capable of detecting the target miR-29a specifically with high selectivity. These results suggest that this solution-based SERS platform has a significant capability for simple, sensitive, and selective miR-29a analysis.
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Affiliation(s)
- Kiatnida Treerattrakoon
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand.
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, UK
| | - Pimporn Roeksrungruang
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand.
| | - Tararaj Dharakul
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Deanpen Japrung
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand.
| | - Karen Faulds
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, UK
| | - Duncan Graham
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, UK
| | - Suwussa Bamrungsap
- National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand.
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13
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Di Gioacchino M, Della Valle L, Allegra A, Pioggia G, Gangemi S. AllergoOncology: Role of immune cells and immune proteins. Clin Transl Allergy 2022; 12:e12133. [PMID: 35344301 PMCID: PMC8967267 DOI: 10.1002/clt2.12133] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 12/21/2021] [Accepted: 02/18/2022] [Indexed: 12/13/2022] Open
Abstract
Background Immune cells and immune proteins play a pivotal role in host responses to pathogens, allergens and cancer. Understanding the crosstalk between allergic response and cancer, immune surveillance, immunomodulation, role of immunoglobulin E (IgE)‐mediated functions and help to develop novel therapeutic strategies. Allergy and oncology show two opposite scenarios: whereas immune tolerance is desired in allergy, it is detrimental in cancer. Aim The current review provides an update on the role of immune cells and immune proteins in allergy and cancer fields. Methods Authors investigated the role of relevant immunological markers and the correlation with cancer progression or cancer suppression. Results Activated immune cells such as macrophages ‘M1’, dendritic cells (DCs), innate lymphoid cells (ILC2), NK cells, Th1, follicular T helper cells (TFH), TCD8+, B lymphocytes and eosinophils have inhibitory effects on tumourigenesis, while tolerogenic cells such as macrophages ‘M2,’ tolerogenic DCs, ILC3, T and B regulatory lymphocytes appear to favour carcinogenesis. Mastocytes and alarmins can have both effects. RIgE antibodies and CCCL5 chemokine have an anticancer role, whereas IgG4, free light chains, Il‐10, TGF‐β, lipocalin‐2, CCL1 chemokine promote cancer progression. Fundamental is also the contribution of epigenetic changes regulated by the microRNA in cancer progression. Conclusion This knowledge represents the key to developing new anticancer therapies.
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Affiliation(s)
- Mario Di Gioacchino
- Center for Advanced Science and Technology, G. d'Annunzio University, Chieti, Italy.,IDA - Institute of Clinical Immunotherapy and Advanced Biological Treatments, Pescara, Italy
| | - Loredana Della Valle
- Center for Advanced Science and Technology, G. d'Annunzio University, Chieti, Italy.,IDA - Institute of Clinical Immunotherapy and Advanced Biological Treatments, Pescara, Italy
| | - Alessandro Allegra
- Division of Hematology, Department of Human Pathology in Adulthood and Childhood 'Gaetano Barresi', University of Messina, Messina, Italy
| | - Giovanni Pioggia
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Messina, Italy
| | - Sebastiano Gangemi
- Department of Clinical and Experimental Medicine, School of Allergy and Clinical Immunology, and Operative Unit of Allergy and Clinical Immunology, University of Messina, Messina, Italy
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14
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He X, Pan W. Host–parasite interactions mediated by cross-species microRNAs. Trends Parasitol 2022; 38:478-488. [DOI: 10.1016/j.pt.2022.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/21/2022] [Accepted: 02/21/2022] [Indexed: 10/18/2022]
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15
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Shaw P, Lokhotiya K, Kumarasamy C, Sunil K, Suresh D, Shetty S, Muthukaliannan GK, Baxi S, Mani RR, Sivanandy P, Chandramoorthy HC, Gupta MM, Samiappan S, Jayaraj R. Mapping Research on miRNAs in Cancer: A Global DataAnalysis and Bibliometric Profiling Analysis. PATHOPHYSIOLOGY 2022; 29:66-80. [PMID: 35366290 PMCID: PMC8950962 DOI: 10.3390/pathophysiology29010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 01/31/2022] [Accepted: 02/08/2022] [Indexed: 11/16/2022] Open
Abstract
miRNAs biomarkers are emerging as an essential part of clinical oncology. Their oncogenic and tumour suppressor properties playing a role in malignancy has generated interest in their potential for use in disease prognosis. While several studies on miRNA have been carried out across the globe, evaluating the clinical implications of miRNAs in cancer diagnosis and prognosis research has currently not been attempted. A study delineating the area of miRNA research, including the topics presently being focused on, the seminal papers in this field, and the direction of research interest, does not exist. This study aims to conduct a large-scale, global data analysis and bibliometric profiling analysis of studies to evaluate the research output of clinical implications of miRNAs in cancer diagnosis and prognosis listed in the SCOPUS database. A systematic search strategy was followed to identify and extract all relevant studies, subsequently analysed to generate a bibliometric map. SPSS software (version 27) was used to calculate bibliometric indicators or parameters for analysis, such as year and country of affiliation with leading authors, journals, and institutions. It is also used to analyse annual research outputs, including total citations and the number of times it has been cited with productive nations and H-index. The number of global research articles retrieved for miRNA-Cancer research over the study period 2003 to 2019 was 18,636. Between 2012 and 2019, the growth rate of global publications is six times (n = 15,959; 90.71 percent articles) that of 2003 to 2011. (2704; 9.29 per cent articles). China published the most publications in the field of miRNA in cancer (n = 7782; 41%), while the United States had the most citations (n = 327,538; 48%) during the time span. Of these journals, Oncotarget has the highest percentage of article publications. The journal Cancer Research had the most citations (n = 41,876), with 6.20 per cent (n = 41,876). This study revealed a wide variety of journals in which miRNA-Cancer research are published; these bibliometric parameters exhibit crucial clinical information on performance assessment of research productivity and quality of research output. Therefore, this study provides a helpful reference for clinical oncologists, cancer scientists, policy decision-makers and clinical data researchers.
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Affiliation(s)
- Peter Shaw
- Oujiang Laboratory, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China;
- Menzies School of Health Research, Darwin 0810, Australia
| | - Kartik Lokhotiya
- School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India; (K.L.); (G.K.M.)
| | - Chellan Kumarasamy
- School of Health and Medical Sciences, Curtin University, Perth 6102, Australia;
| | - Krishnan Sunil
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA;
| | - Deepa Suresh
- Division of Endocrinology, Department of Internal Medicine, Mayo Clinic Florida, Jacksonville, FL 32224, USA;
| | - Sameep Shetty
- Department of Oral and Maxillofacial Surgery, Manipal College of Dental Sciences, Mangalore, Manipal Academy of Higher Education, A Constituent of MAHE, Manipal 576104, India;
| | | | - Siddhartha Baxi
- Genesis Care Gold Coast Radiation Oncologist, John Flynn Hospital, Tugun 4224, Australia;
| | - Ravishankar Ram Mani
- Department of Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia;
| | - Palanisamy Sivanandy
- Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia;
| | - Harish C. Chandramoorthy
- Stem Cells and Regenerative Medicine Unit, Department of Microbiology and Clinical Parasitology, College of Medicine, King Khalid University, Abha 56000, Saudi Arabia;
| | - Madan Mohan Gupta
- School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine 3303, Trinidad and Tobago;
| | - Suja Samiappan
- Department of Biochemistry, Bharathiar University, Coimbatore 641046, India;
| | - Rama Jayaraj
- Northern Territory Institute of Research and Training, Tiwi 0810, Australia
- Correspondence:
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16
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Hamidi AA, Zangoue M, Kashani D, Zangouei AS, Rahimi HR, Abbaszadegan MR, Moghbeli M. MicroRNA-217: a therapeutic and diagnostic tumor marker. Expert Rev Mol Diagn 2021; 22:61-76. [PMID: 34883033 DOI: 10.1080/14737159.2022.2017284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Cancer as one of the most common causes of death has always been one of the major health challenges globally. Since, the identification of tumors in the early tumor stages can significantly reduce mortality rates; it is required to introduce novel early detection tumor markers. MicroRNAs (miRNAs) have pivotal roles in regulation of cell proliferation, migration, apoptosis, and tumor progression. Moreover, due to the higher stability of miRNAs than mRNAs in body fluids, they can be considered as non-invasive diagnostic or prognostic markers in cancer patients. AREAS COVERED In the present review we have summarized the role of miR-217 during tumor progressions. The miR-217 functions were categorized based on its target molecular mechanisms and signaling pathways. EXPERT OPINION It was observed that miR-217 mainly exerts its function by regulation of the transcription factors during tumor progressions. The WNT, MAPK, and PI3K/AKT signaling pathways were also important molecular targets of miR-217 in different cancers. The present review clarifies the molecular biology of miR-217 and paves the way of introducing miR-217 as a non-invasive diagnostic marker and therapeutic target in cancer therapy.
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Affiliation(s)
- Amir Abbas Hamidi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Malihe Zangoue
- Department of Anesthesiology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Daniel Kashani
- Department of Internal Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA
| | - Amir Sadra Zangouei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Reza Rahimi
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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17
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Dell'Olio F. Multiplexed Liquid Biopsy and Tumor Imaging Using Surface-Enhanced Raman Scattering. BIOSENSORS 2021; 11:449. [PMID: 34821665 PMCID: PMC8615571 DOI: 10.3390/bios11110449] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/09/2021] [Accepted: 11/10/2021] [Indexed: 06/13/2023]
Abstract
The recent improvements in diagnosis enabled by advances in liquid biopsy and oncological imaging significantly better cancer care. Both these complementary approaches, which are used for early tumor detection, characterization, and monitoring, can benefit from applying techniques based on surface-enhanced Raman scattering (SERS). With a detection sensitivity at the single-molecule level, SERS spectroscopy is widely used in cell and molecular biology, and its capability for the in vitro detection of several types of cancer biomarkers is well established. In the last few years, several intriguing SERS applications have emerged, including in vivo imaging for tumor targeting and the monitoring of drug release. In this paper, selected recent developments and trends in SERS applications in the field of liquid biopsy and tumor imaging are critically reviewed, with a special emphasis on results that demonstrate the clinical utility of SERS.
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Affiliation(s)
- Francesco Dell'Olio
- Department of Electrical and Information Engineering, Polytechnic University of Bari, 70125 Bari, Italy
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18
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Kersy O, Salmon-Divon M, Shpilberg O, Hershkovitz-Rokah O. Non-Coding RNAs in Normal B-Cell Development and in Mantle Cell Lymphoma: From Molecular Mechanism to Biomarker and Therapeutic Agent Potential. Int J Mol Sci 2021; 22:ijms22179490. [PMID: 34502399 PMCID: PMC8430640 DOI: 10.3390/ijms22179490] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/23/2021] [Accepted: 08/29/2021] [Indexed: 12/27/2022] Open
Abstract
B-lymphocytes are essential for an efficient immune response against a variety of pathogens. A large fraction of hematologic malignancies are of B-cell origin, suggesting that the development and activation of B cells must be tightly regulated. In recent years, differentially expressed non-coding RNAs have been identified in mantle cell lymphoma (MCL) tumor samples as opposed to their naive, normal B-cell compartment. These aberrantly expressed molecules, specifically microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), have a role in cellular growth and survival pathways in various biological models. Here, we provide an overview of current knowledge on the role of non-coding RNAs and their relevant targets in B-cell development, activation and malignant transformation, summarizing the current understanding of the role of aberrant expression of non-coding RNAs in MCL pathobiology with perspectives for clinical use.
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Affiliation(s)
- Olga Kersy
- Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel; (O.K.); (M.S.-D.)
- Translational Research Lab, Assuta Medical Centers, Tel-Aviv 6971028, Israel;
| | - Mali Salmon-Divon
- Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel; (O.K.); (M.S.-D.)
- Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Ofer Shpilberg
- Translational Research Lab, Assuta Medical Centers, Tel-Aviv 6971028, Israel;
- Adelson School of Medicine, Ariel University, Ariel 40700, Israel
- Institute of Hematology, Assuta Medical Centers, Tel-Aviv 6971028, Israel
| | - Oshrat Hershkovitz-Rokah
- Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel; (O.K.); (M.S.-D.)
- Translational Research Lab, Assuta Medical Centers, Tel-Aviv 6971028, Israel;
- Correspondence: ; Tel.: +972-3-764-4094
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19
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Zhang S, Wang B, Zheng L, Fu Z, Fu Y, Huang W, Cheng A. Advances in research on microRNAs related to the invasion and metastasis of nasopharyngeal carcinoma. Curr Mol Pharmacol 2021; 15:463-474. [PMID: 34126919 DOI: 10.2174/1874467214666210614150720] [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: 09/05/2020] [Revised: 01/22/2021] [Accepted: 02/22/2021] [Indexed: 12/24/2022]
Abstract
Nasopharyngeal carcinoma (NPC), which is associated with latent Epstein-Barr virus infection in most cases, is a unique epithelial malignancy arising from the nasopharyngeal mucosal lining. Accumulating evidence provides insights into the genetic and molecular aberrations that likely drive nasopharyngeal tumor development and progression. We review recent analyses of microRNAs (miRNAs), including Epstein-Barr virus-encoded miRNAs (EBV-encoded miRNAs) and dysregulated cellular miRNAs, that may be related to the metastasis of nasopharyngeal carcinoma. The studies summarized herein have greatly expanded our knowledge of the molecular biology of NPC involving miRNAs, and they may provide new biological targets for clinical diagnosis and reveal the potential of microRNA therapeutics. However, much information remains to be uncovered.
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Affiliation(s)
- ShanShan Zhang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang School of Medicine, University of South China, Hengyang, Hunan 421001, China
| | - BaiQi Wang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang School of Medicine, University of South China, Hengyang, Hunan 421001, China
| | - LuLu Zheng
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang School of Medicine, University of South China, Hengyang, Hunan 421001, China
| | - ZhuQiong Fu
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang School of Medicine, University of South China, Hengyang, Hunan 421001, China
| | - YiTing Fu
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang School of Medicine, University of South China, Hengyang, Hunan 421001, China
| | - WeiGuo Huang
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang School of Medicine, University of South China, Hengyang, Hunan 421001, China
| | - AiLan Cheng
- Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, Hengyang School of Medicine, University of South China, Hengyang, Hunan 421001, China
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20
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Zangouei AS, Moghbeli M. MicroRNAs as the critical regulators of cisplatin resistance in gastric tumor cells. Genes Environ 2021; 43:21. [PMID: 34099061 PMCID: PMC8182944 DOI: 10.1186/s41021-021-00192-4] [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: 02/20/2021] [Accepted: 05/24/2021] [Indexed: 12/13/2022] Open
Abstract
Combined chemotherapeutic treatment is the method of choice for advanced and metastatic gastric tumors. However, resistance to chemotherapeutic agents is one of the main challenges for the efficient gastric cancer (GC) treatment. Cisplatin (CDDP) is used as an important regimen of chemotherapy for GC which induces cytotoxicity by interfering with DNA replication in cancer cells and inducing their apoptosis. Majority of patients experience cisplatin-resistance which is correlated with tumor metastasis and relapse. Moreover, prolonged and high-dose cisplatin administrations cause serious side effects such as nephrotoxicity, ototoxicity, and anemia. Since, there is a high rate of recurrence after CDDP treatment in GC patients; it is required to clarify the molecular mechanisms associated with CDDP resistance to introduce novel therapeutic methods. There are various cell and molecular processes associated with multidrug resistance (MDR) including drug efflux, detoxification, DNA repair ability, apoptosis alteration, signaling pathways, and epithelial-mesenchymal transition (EMT). MicroRNAs are a class of endogenous non-coding RNAs involved in chemo resistance of GC cells through regulation of all of the MDR mechanisms. In present review we have summarized all of the miRNAs associated with cisplatin resistance based on their target genes and molecular mechanisms in gastric tumor cells. This review paves the way of introducing a miRNA-based panel of prognostic markers to improve the efficacy of chemotherapy and clinical outcomes in GC patients. It was observed that miRNAs are mainly involved in cisplatin response of gastric tumor cells via regulation of signaling pathways, autophagy, and apoptosis.
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Affiliation(s)
- Amir Sadra Zangouei
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Meysam Moghbeli
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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21
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Zhou P, Gong S, Liu B, Shi M, Lu F, Li N, Tang B. A hybridization-based dual-colorimetric kit for circulating cancer miRNA detection. Chem Commun (Camb) 2021; 57:6058-6061. [PMID: 34037012 DOI: 10.1039/d1cc01607e] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
A dual-colorimetric miRNA detection kit that can simultaneously detect two miRNAs with high sensitivity and selectivity is developed, and the data can be read by the naked eye easily. The kit is able to distinguish the patients from healthy people and achieve lung cancer diagnosis using clinical serum samples in a short time.
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Affiliation(s)
- Ping Zhou
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
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22
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Baber S, Bayat M, Mohamadnia A, Shamshiri A, Amini Shakib P, Bahrami N. Role of miR153 and miR455-5p Expression in Oral Squamous Cell Carcinoma Isolated from Plasma. Asian Pac J Cancer Prev 2021; 22:157-161. [PMID: 33507694 PMCID: PMC8184173 DOI: 10.31557/apjcp.2021.22.1.157] [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: 09/19/2020] [Indexed: 12/20/2022] Open
Abstract
Background: Despite the notable advances in modern surgery and radiotherapy,no significant increase in the five year survival rate of oral squamous cell carcinoma has been reported. Collecting evidence demonstrates that miR 153 and miR 455-5p play a key role in growth and progression of oral cancer. Early detection of OSCC is important for enhancing patient quality of life and clinical treatment.For this reason, biomarkers or tumour markers offer an opportunity to intervene and avoid development of oral cancer. Methods: A total of 50 blood samples from patients from both genders (25 OSCC and 25 healthy people/control groups) were obtained to determine the expression of miR153 and miR455-5p using Real time Polymerase chain reaction and t test. Results: In general by using the formula Δ ct, it is evident that the miR 153 expression in peripheral blood is lower in patients than in healthy individuals (1.97) while the miR 455-5p expression in peripheral blood is higher in patients than in healthy individuals (2.56). Conclusion: We conclude that miR153 and miR 455-5p expression in serum can function as a diagnostic screening test for the early detection of oral squamous cell carcinoma.
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Affiliation(s)
- Sajad Baber
- Department of Oral and Maxillofacial Surgery, School of Dentistry, International Campus, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohamad Bayat
- Department of Oral and Maxillofacial Surgery, School of Dentistry, International Campus, Tehran University of Medical Sciences, Tehran, Iran.,Craniomaxillofacial Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdolreza Mohamadnia
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ahmadreza Shamshiri
- Research Center for Caries Prevention, Dentistry Research Institute, Department of Community Oral Health, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Pouyan Amini Shakib
- Department of pathology School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
| | - Naghmeh Bahrami
- Craniomaxillofacial Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Mar-Aguilar F, Arreola-Triana A, Mata-Cardona D, Gonzalez-Villasana V, Rodríguez-Padilla C, Reséndez-Pérez D. Evidence of transfer of miRNAs from the diet to the blood still inconclusive. PeerJ 2020; 8:e9567. [PMID: 32995073 PMCID: PMC7502231 DOI: 10.7717/peerj.9567] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 06/28/2020] [Indexed: 12/13/2022] Open
Abstract
MicroRNAs (miRNAs) are short, non-coding, single-strand RNA molecules that act as regulators of gene expression in plants and animals. In 2012, the first evidence was found that plant miRNAs could enter the bloodstream through the digestive tract. Since then, there has been an ongoing discussion about whether miRNAs from the diet are transferred to blood, accumulate in tissues, and regulate gene expression. Different research groups have tried to replicate these findings, using both plant and animal sources. Here, we review the evidence for and against the transfer of diet-derived miRNAs from plants, meat, milk and exosome and their assimilation and putative molecular regulation role in the consuming organism. Some groups using both miRNAs from plant and animal sources have claimed success, whereas others have not shown transfer. In spite of the biological barriers that may limit miRNA transference, several diet-derived miRNAs can transfer into the circulating system and targets genes for transcription regulation, which adds arguments that miRNAs can be absorbed from the diet and target specific genes by regulating their expression. However, many other studies show that cross-kingdom transfer of exogenous miRNAs appears to be insignificant and not biologically relevant. The main source of controversy in plant studies is the lack of reproducibility of the findings. For meat-derived miRNAs, studies concluded that the miRNAs can survive the cooking process; nevertheless, our evidence shows that the bovine miRNAs are not transferred to human bloodstream. The most important contributions and promising evidence in this controversial field is the transference of milk miRNAs in exosomes and the finding that plant miRNAs in beebread regulate honeybee caste development, and cause similar changes when fed to Drosophila. MiRNAs encapsulated in exosomes ensure their stability and resistance in the harsh conditions presented in milk, bloodstream, and gastrointestinaltract to reinforce the idea of transference. Regardless of the model organism, the idea of source of miRNAs, or the approach-bioinformatics or in vivo-the issue of transfer of miRNAs from the diet remains in doubt. Our understanding of the cross-kingdom talk of miRNAs needs more research to study the transfer of "xenomiRs" from different food sources to complement and expand what we know so far regarding the interspecies transfer of miRNAs.
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Affiliation(s)
- Fermín Mar-Aguilar
- Facultad de Ciencias Biológicas, Biología Celular y Genética, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - Alejandra Arreola-Triana
- Facultad de Ciencias Biológicas, Biología Celular y Genética, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - Daniela Mata-Cardona
- Facultad de Ciencias Biológicas, Departamento de Inmunología y Virología, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - Vianey Gonzalez-Villasana
- Facultad de Ciencias Biológicas, Biología Celular y Genética, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - Cristina Rodríguez-Padilla
- Facultad de Ciencias Biológicas, Departamento de Inmunología y Virología, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
| | - Diana Reséndez-Pérez
- Facultad de Ciencias Biológicas, Biología Celular y Genética, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
- Facultad de Ciencias Biológicas, Departamento de Inmunología y Virología, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, Mexico
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Huang D, Ou W, Tong H, Peng M, Ou Y, Song Z. Analysis of the expression levels and clinical value of miR-365 and miR-25 in serum of patients with non-small cell lung cancer. Oncol Lett 2020; 20:191. [PMID: 32952660 PMCID: PMC7479530 DOI: 10.3892/ol.2020.12053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 01/22/2020] [Indexed: 12/20/2022] Open
Abstract
The present study aimed to investigate the expression levels and clinical value of miR-365 and miR-25 in serum of patients with non-small cell lung cancer (NSCLC). Patients (180) diagnosed with NSCLC at the Affiliated Hospital of Guangdong Medical University from July 2011 to December 2013 were used as the experimental group. Volunteers (90) undergoing health examinations were used as the control group. The serum of the patients was collected after fasting in the morning. The expression levels of miR-365 and miR-25 in the serum of patients was assessed by quantitative real-time PCR (qRT-PCR), and the relationship among miR-365, miR-25 and the postoperative survival rate of NSCLC patients was analyzed. The relative expression level of miR-25 of patients with peripheral infiltration was significantly higher than that of patients without peripheral infiltration (P<0.05). There were significant differences in the relative expression level of miR-25 in different pathological grades and TNM stages, as well as with lymph node metastasis (P<0.05). The survival rate of NSCLC patients with high expression of miR-25 was significantly lower than that of NSCLC patients with low expression of miR-25 (P<0.05). The relative expression level of miR-365 of patients with peripheral infiltration was significantly lower than that of patients without peripheral infiltration (P<0.05). There were significant differences in the relative expression level of miR-365 in different pathological grades and TNM stages, as well as with lymph node metastasis (P<0.05). The survival rate of NSCLC patients with high expression of miR-365 was significantly higher than that of NSCLC patients with low expression of miR-365 (P<0.05). In conclusion, the expression levels of miR-25 and miR-365 were different in the serum of NSCLC patients, and they were closely related to certain clinical characteristics such as peripheral infiltration, pathological grade, tumor diameter, TNM stage and lymph node metastasis. Moreover, it was revealed that miR-25 and miR-365 affected the 5-year survival rate of patients. miR-25 and miR-365 could be used as important tumor markers to evaluate the prognosis of NSCLC patients.
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Affiliation(s)
- Dongxuan Huang
- Department of Respiratory Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, P.R. China
| | - Wenfang Ou
- Department of Respiratory Medicine, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, Guangdong 518110, P.R. China
| | - Huifen Tong
- Department of Respiratory Medicine, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, Guangdong 518110, P.R. China
| | - Ming Peng
- Department of Respiratory Medicine, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, Guangdong 518110, P.R. China
| | - Yamei Ou
- Department of Respiratory Medicine, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, Guangdong 518110, P.R. China
| | - Zeqing Song
- Department of Respiratory Medicine, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, Guangdong 518110, P.R. China
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25
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Wardana T, Gunawan L, Herawati C, Oktriani R, Anwar SL, Astuti I, Aryandhono T, Mubarika S. Circulation EBV Mir-Bart-7 Relating to Clinical Manifestation in Nasopharyngeal Carcinoma. Asian Pac J Cancer Prev 2020; 21:2777-2782. [PMID: 32986380 PMCID: PMC7779452 DOI: 10.31557/apjcp.2020.21.9.2777] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 09/25/2020] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE Nasopharyngeal Carcinoma (NPC) is an endemic head and neck malignancy in Asia Pacific regions that is associated with chronic infection by Epstein-Barr virus (EBV). EBV miR-BART-7 is a microRNA (miRNA) encoded by EBV that regulates malignant behavior of NPC. However, the role and function of miR-BART7 are not clear, particularly the relation of circulating levels and patient's clinical presentation. METHODS Circulating miR-BART-7 levels were measured by using qRT-PCR and were correlated with clinical and pathological data. RESULT Of 52 NPC patients included in this study, 85% were diagnosed in the late stages (Stage III-IV). 73% of tumors were non-keratinizing undifferentiated NPC, 92% of tumors were WHO class III histology and all cases were EBV-IgA positive. Over-expression of miR-BART7-3p was correlated with positive regional lymph nodes in newly diagnosed (4.61 fold changes, p <0.05). CONCLUSION Over-expression of circulating EBV miR-BART7 correlated with positive regional lymph nodes reflecting the diagnostic and prognostic values of circulating miR-BART7 for patients with NPC.
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Affiliation(s)
- Tirta Wardana
- Department of Biomedicine, School of Dentistry, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Indonesia.
| | - Lisa Gunawan
- Postgraduate Student, Center for Biotechnology, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Cita Herawati
- Department of Ear, Nose and Throat, Dharmais National Cancer Hospital, Jakarta, Indonesia.
| | - Risky Oktriani
- Department of Biochemistry, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Sumadi Lukman Anwar
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Indwiani Astuti
- Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Teguh Aryandhono
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
| | - Sofia Mubarika
- Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
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26
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Terrinoni A, Calabrese C, Basso D, Aita A, Caporali S, Plebani M, Bernardini S. The circulating miRNAs as diagnostic and prognostic markers. Clin Chem Lab Med 2020; 57:932-953. [PMID: 30838832 DOI: 10.1515/cclm-2018-0838] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Accepted: 10/23/2018] [Indexed: 02/07/2023]
Abstract
A large portion of the human genome transcribes RNA sequences that do not code for any proteins. The first of these sequences was identified in 1993, and the best known noncoding RNAs are microRNA (miRNAs). It is now fully established that miRNAs regulate approximately 30% of the known genes that codify proteins. miRNAs are involved in several biological processes, like cell proliferation, differentiation, apoptosis and metastatization. These RNA products regulate gene expression at the post-transcriptional level, modulating or inhibiting protein expression by interacting with specific sequences of mRNAs. Mature miRNAs can be detected in blood plasma, serum and also in a wide variety of biological fluids. They can be found associated with proteins, lipids as well as enclosed in exosome vesicles. We know that circulating miRNAs (C-miRNAs) can regulate several key cellular processes in tissues different from the production site. C-miRNAs behave as endogenous mediators of RNA translation, and an extraordinary knowledge on their function has been obtained in the last years. They can be secreted in different tissue cells and associated with specific pathological conditions. Significant evidence indicates that the initiation and progression of several pathologies are "highlighted" by the presence of specific C-miRNAs, underlining their potential diagnostic relevance as clinical biomarkers. Here we review the current literature on the possible use of this new class of molecules as clinical biomarkers of diseases.
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Affiliation(s)
- Alessandro Terrinoni
- Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy
| | - Cosimo Calabrese
- Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Daniela Basso
- Department of Medicine - DIMED; Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Ada Aita
- Department of Medicine - DIMED; Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Sabrina Caporali
- Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Mario Plebani
- Department of Medicine - DIMED; Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy
| | - Sergio Bernardini
- Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
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27
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Cho H, Hwang M, Hong EH, Yu H, Park HH, Koh SH, Shin YU. Micro-RNAs in the aqueous humour of patients with diabetic macular oedema. Clin Exp Ophthalmol 2020; 48:624-635. [PMID: 32173975 DOI: 10.1111/ceo.13750] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 02/25/2020] [Accepted: 03/11/2020] [Indexed: 02/06/2023]
Abstract
IMPORTANCE Micro-RNAs (miRNAs) have been studied as new biomarkers or mediators in various diseases, but the value of aqueous humour (AH) miRNAs in diabetic macular oedema (DMO) is still not known. BACKGROUND To compare AH miRNAs and related cytokine expression in DMO patients and healthy controls. DESIGN Prospective cross-sectional study. PARTICIPANTS Twenty naïve DMO patients and 13 control subjects, who were scheduled for intravitreal injection and cataract surgery, respectively. METHODS AH samples were collected at the beginning of each procedure and analysed using a miRNA polymerase chain reaction (PCR) array composed of 84 miRNAs, reverse transcripase-quantitative PCR (qPCR) for verifying selected differentially expressed miRNAs, and a cytokine assay, the results of which were compared with bioinformatics conducted to find out genes associated with DMO-related miRNAs. MAIN OUTCOMES MEASURES AH expression of miRNAs and cytokines and the bioinformatics results. RESULTS Five miRNAs (hsa-miR-185-5p, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-15b-5p and hsa-miR-15a-5p) showing a fold change greater than -50 in log2 values in the miRNA PCR array were selected, all significantly down-regulated in the DMO group compared to the control group (P < .05), and showed a direct relationship with tumour necrosis factor, nuclear factor kappa B subunit 1 and interleukin-6 (IL-6) in bioinformatics analysis, all of which were related to vascular endothelial growth factor (VEGF). In the cytokine assay, the aqueous concentrations of VEGF, placental growth factor, IL-6 and IL-8 were significantly higher in the DMO group compared to the control group. CONCLUSIONS AND RELEVANCE This study is the first to perform miRNA profiling of the AH of DMO patients. We identified differentially expressed miRNAs in DMO AH, which may be used as potential biomarkers or novel therapeutic targets for DMO.
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Affiliation(s)
- Heeyoon Cho
- Department of Ophthalmology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Mina Hwang
- Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Eun H Hong
- Department of Ophthalmology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Hyoseon Yu
- Department of Ophthalmology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Hyun-Hee Park
- Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Seong-Ho Koh
- Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea.,Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, Korea
| | - Yong U Shin
- Department of Ophthalmology, Hanyang University College of Medicine, Seoul, Republic of Korea
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28
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Kashyap D, Kaur H. Cell-free miRNAs as non-invasive biomarkers in breast cancer: Significance in early diagnosis and metastasis prediction. Life Sci 2020; 246:117417. [PMID: 32044304 DOI: 10.1016/j.lfs.2020.117417] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/28/2020] [Accepted: 02/05/2020] [Indexed: 02/07/2023]
Abstract
Breast cancer is one of the genetic diseases causing a high mortality among women around the world. Despite the availability of advanced diagnostic tools and treatment strategies, the incidence of breast cancer is increasing every year. This is due to the lack of accurate and reliable biomarkers whose deficiency creates difficulty in early breast cancer recognition, subtypes determination, and metastasis prophecy. Although biomarkers such as ER, PR, Her2, Ki-67, and other genetic platforms e.g. MammaPrint®, Oncotype DX®, Prosigna® or EndoPredict® are available for determination of breast cancer diagnosis and prognosis. However, pertaining to heterogeneous nature, lack of sensitivity, and specificity of these markers, it is still incessant to overcome breast cancer burden. Therefore, a novel biomarker is urgently needed for therapeutic diagnosis and improving prognosis. Lately, it has become more evident that cell-free miRNAs might be useful as good non-invasive biomarkers that are associated with different events in carcinogenesis. For example, some known biomarkers such as miR-21, miR-23a, miR-34a are associated with molecular subtyping and different biomolecular aspects i.e. apoptosis, angiogenesis, metastasis, and miR-1, miR-10b, miR-16 are associated with drug response. Cell-free miRNAs present in human body fluids have proven to be potential biomarkers with significant prognostic and predictive values. Numerous studies have found a distinct expression profile of circulating miRNAs in breast tumour versus non-tumour and in early and advanced-stage, thus implicating its clinical relevance. This review article will highlight the importance of different cell-free miRNAs as a biomarker for early breast cancer detection, subtype classification, and metastasis forecast.
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Affiliation(s)
- Dharambir Kashyap
- Department of Histopathology, Postgraduation Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Harmandeep Kaur
- Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
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29
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Nik Mohamed Kamal NNSB, Shahidan WNS. Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers? Front Pharmacol 2020; 10:1500. [PMID: 32038230 PMCID: PMC6984169 DOI: 10.3389/fphar.2019.01500] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 11/19/2019] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are a group of small non-coding RNAs with approximately 19–25 nucleotides that are involved in regulating a range of developmental and physiological processes. Non-exosomal circulating and exosomal miRNAs have also been proposed to be useful in diagnostics as biomarkers for diseases and different types of cancer. In this review, the quantity of miRNAs and of reliable experimental data analyses of miRNAs that come from exosomal and non-exosomal sources are discussed from the perspective of their use as biomarkers for cancer and other diseases, including viral infections, nervous system disorders, cardiovascular disorders, and diabetes. We summarize other research findings regarding the use of miRNA from these two sources as biomarkers in diagnostics and clinical use. The challenges in using miRNA from these two sources in cancer and disease diagnostics are evaluated and discussed. Validation of specific miRNA signatures as biomarkers is a critical milestone in diagnostics.
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Affiliation(s)
| | - Wan Nazatul Shima Shahidan
- Craniofacial Science Laboratory, School of Dental Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Malaysia
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30
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Kosela-Paterczyk H, Paziewska A, Kulecka M, Balabas A, Kluska A, Dabrowska M, Piatkowska M, Zeber-Lubecka N, Ambrozkiewicz F, Karczmarski J, Mikula M, Rutkowski P, Ostrowski J. Signatures of circulating microRNA in four sarcoma subtypes. J Cancer 2020; 11:874-882. [PMID: 31949491 PMCID: PMC6959019 DOI: 10.7150/jca.34723] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Accepted: 09/27/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Sarcomas are rare malignant tumors of mesenchymal origin. The discovery of circulating biomarkers with high diagnostic value could supplement diagnosis of this heterogenous group of tumors. The aim of this study was to identify the profiles of circulating miRNA (c-miRNAs) in four groups of common bone and soft tissue sarcomas. Methods: At the time of diagnosis, blood samples were collected from 86 patients: 36 with locally advanced/unresectable/metastatic gastrointestinal stromal tumor (GIST) who received first-line treatment with imatinib; 16 with locally advanced osteosarcoma (OS); 26 with locally advanced synovial sarcoma (SS); and eight with locally advanced Ewing sarcoma (ES). In addition, samples were collected from 30 healthy controls. C-miRNAs were isolated using a miRCURY RNA Isolation Kit, followed by preparation of cDNA libraries and sequencing on the Ion Proton platform. Results: Pair-wise comparisons identified 156 unique c-miRNAs (adjusted P-value < 0.05) showing significant dysregulation between controls and patients; of these, 24, 36, 42, and 99 differentiated controls from pretherapeutic OS, SS, ES, and GIST, respectively. Ten c-miRNAs were commonly altered in at least three sarcoma types. Receiver operating characteristic curves and area under the curve (ROC-AUC) analyses revealed that a four-miRNA diagnostic classifier was able to differentiate controls from ES, GIST, OS, and SS, with AUC-ROC values of 1, 0.97, 0.95, and 0.94, respectively. Conclusions: Aberrant miRNA expression signatures were identified in serum from patients with four different sarcoma subtypes. Differences in miRNA expression profiles between sarcoma patients and healthy volunteers suggest that miRNAs may play a role in sarcoma development.
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Affiliation(s)
- Hanna Kosela-Paterczyk
- Department of Soft Tissue, Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute - Oncology Centre, Warsaw, Poland
| | - Agnieszka Paziewska
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Maria Kulecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Aneta Balabas
- Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Anna Kluska
- Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Michalina Dabrowska
- Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Magdalena Piatkowska
- Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Natalia Zeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Filip Ambrozkiewicz
- Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Jakub Karczmarski
- Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
| | - Piotr Rutkowski
- Department of Soft Tissue, Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute - Oncology Centre, Warsaw, Poland
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Department of Genetics, Maria Sklodowska-Curie Institute - Oncology Centre; 02-781 Warsaw, Poland
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31
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Mannavola F, D’Oronzo S, Cives M, Stucci LS, Ranieri G, Silvestris F, Tucci M. Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression. Int J Mol Sci 2019; 21:E52. [PMID: 31861757 PMCID: PMC6981648 DOI: 10.3390/ijms21010052] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 12/11/2019] [Accepted: 12/18/2019] [Indexed: 12/21/2022] Open
Abstract
Cutaneous melanoma shows a high metastatic potential based on its ability to overcome the immune system's control. The mechanisms activated for these functions vary extremely and are also represented by the production of a number of extracellular vesicles including exosomes. Other vesicles showing a potential role in the melanoma progression include oncosomes and melanosomes and the majority of them mediate tumor processes including angiogenesis, immune regulation, and modifications of the micro-environment. Moreover, a number of epigenetic modifications have been described in melanoma and abundant production of altered microRNAs (mi-RNAs), non-coding RNAs, histones, and abnormal DNA methylation have been associated with different phases of melanoma progression. In addition, exosomes, miRNAs, and other molecular factors have been used as potential biomarkers reflecting disease evolution while others have been suggested to be potential druggable molecules for therapeutic application.
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Affiliation(s)
- Francesco Mannavola
- Department of Biomedical Sciences and Clinical Oncology, University of Bari, ‘Aldo Moro’, 70121 Bari, Italy; (F.M.); (S.D.); (M.C.); (L.S.S.); (F.S.)
| | - Stella D’Oronzo
- Department of Biomedical Sciences and Clinical Oncology, University of Bari, ‘Aldo Moro’, 70121 Bari, Italy; (F.M.); (S.D.); (M.C.); (L.S.S.); (F.S.)
- National Cancer Research Center, Istituto Tumori ‘Giovanni Paolo II’, 70121 Bari, Italy;
| | - Mauro Cives
- Department of Biomedical Sciences and Clinical Oncology, University of Bari, ‘Aldo Moro’, 70121 Bari, Italy; (F.M.); (S.D.); (M.C.); (L.S.S.); (F.S.)
| | - Luigia Stefania Stucci
- Department of Biomedical Sciences and Clinical Oncology, University of Bari, ‘Aldo Moro’, 70121 Bari, Italy; (F.M.); (S.D.); (M.C.); (L.S.S.); (F.S.)
| | - Girolamo Ranieri
- National Cancer Research Center, Istituto Tumori ‘Giovanni Paolo II’, 70121 Bari, Italy;
| | - Franco Silvestris
- Department of Biomedical Sciences and Clinical Oncology, University of Bari, ‘Aldo Moro’, 70121 Bari, Italy; (F.M.); (S.D.); (M.C.); (L.S.S.); (F.S.)
| | - Marco Tucci
- Department of Biomedical Sciences and Clinical Oncology, University of Bari, ‘Aldo Moro’, 70121 Bari, Italy; (F.M.); (S.D.); (M.C.); (L.S.S.); (F.S.)
- National Cancer Research Center, Istituto Tumori ‘Giovanni Paolo II’, 70121 Bari, Italy;
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32
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Dysregulation of miR-638 in Breast Cancer Patients and Bioinformatics Investigation of Its Target Genes in Apoptosis, Angiogenesis and Autophagy Pathways. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2019. [DOI: 10.5812/ijcm.88829] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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33
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Pardini B, Sabo AA, Birolo G, Calin GA. Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies. Cancers (Basel) 2019; 11:E1170. [PMID: 31416190 PMCID: PMC6721601 DOI: 10.3390/cancers11081170] [Citation(s) in RCA: 136] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/04/2019] [Accepted: 08/10/2019] [Indexed: 02/06/2023] Open
Abstract
The last two decades of cancer research have been devoted in two directions: (1) understanding the mechanism of carcinogenesis for an effective treatment, and (2) improving cancer prevention and screening for early detection of the disease. This last aspect has been developed, especially for certain types of cancers, thanks also to the introduction of new concepts such as liquid biopsies and precision medicine. In this context, there is a growing interest in the application of alternative and noninvasive methodologies to search for cancer biomarkers. The new frontiers of the research lead to a search for RNA molecules circulating in body fluids. Searching for biomarkers in extracellular body fluids represents a better option for patients because they are easier to access, less painful, and potentially more economical. Moreover, the possibility for these types of samples to be taken repeatedly, allows a better monitoring of the disease progression or treatment efficacy for a better intervention and dynamic treatment of the patient, which is the fundamental basis of personalized medicine. RNA molecules, freely circulating in body fluids or packed in microvesicles, have all the characteristics of the ideal biomarkers owing to their high stability under storage and handling conditions and being able to be sampled several times for monitoring. Moreover, as demonstrated for many cancers, their plasma/serum levels mirror those in the primary tumor. There are a large variety of RNA species noncoding for proteins that could be used as cancer biomarkers in liquid biopsies. Among them, the most studied are microRNAs, but recently the attention of the researcher has been also directed towards Piwi-interacting RNAs, circular RNAs, and other small noncoding RNAs. Another class of RNA species, the long noncoding RNAs, is larger than microRNAs and represents a very versatile and promising group of molecules which, apart from their use as biomarkers, have also a possible therapeutic role. In this review, we will give an overview of the most common noncoding RNA species detectable in extracellular fluids and will provide an update concerning the situation of the research on these molecules as cancer biomarkers.
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Affiliation(s)
- Barbara Pardini
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy.
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy.
| | - Alexandru Anton Sabo
- Department of Pediatrics, Marie Curie Emergency Clinical Hospital for Children, 077120 Bucharest, Romania
| | - Giovanni Birolo
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy
- Unit of Molecular Epidemiology and Exposome, Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy
| | - George Adrian Calin
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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Single-Step FRET-Based Detection of Femtomoles DNA. SENSORS 2019; 19:s19163495. [PMID: 31405068 PMCID: PMC6719117 DOI: 10.3390/s19163495] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 08/02/2019] [Accepted: 08/05/2019] [Indexed: 12/11/2022]
Abstract
Sensitive detection of nucleic acids and identification of single nucleotide polymorphism (SNP) is crucial in diagnosis of genetic diseases. Many strategies have been developed for detection and analysis of DNA, including fluorescence, electrical, optical, and mechanical methods. Recent advances in fluorescence resonance energy transfer (FRET)-based sensing have provided a new avenue for sensitive and quantitative detection of various types of biomolecules in simple, rapid, and recyclable platforms. Here, we report single-step FRET-based DNA sensors designed to work via a toehold-mediated strand displacement (TMSD) process, leading to a distinct change in the FRET efficiency upon target binding. Using single-molecule FRET (smFRET), we show that these sensors can be regenerated in situ, and they allow detection of femtomoles DNA without the need for target amplification while still using a dramatically small sample size (fewer than three orders of magnitude compared to the typical sample size of bulk fluorescence). In addition, these single-molecule sensors exhibit a dynamic range of approximately two orders of magnitude. Using one of the sensors, we demonstrate that the single-base mismatch sequence can be discriminated from a fully matched DNA target, showing a high specificity of the method. These sensors with simple and recyclable design, sensitive detection of DNA, and the ability to discriminate single-base mismatch sequences may find applications in quantitative analysis of nucleic acid biomarkers.
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Why the Gold Standard Approach by Mammography Demands Extension by Multiomics? Application of Liquid Biopsy miRNA Profiles to Breast Cancer Disease Management. Int J Mol Sci 2019; 20:ijms20122878. [PMID: 31200461 PMCID: PMC6627787 DOI: 10.3390/ijms20122878] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/07/2019] [Accepted: 06/11/2019] [Indexed: 02/06/2023] Open
Abstract
In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the “golden standard” approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.
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Zou X, Wei J, Huang Z, Zhou X, Lu Z, Zhu W, Miao Y. Identification of a six-miRNA panel in serum benefiting pancreatic cancer diagnosis. Cancer Med 2019; 8:2810-2822. [PMID: 31006985 PMCID: PMC6558458 DOI: 10.1002/cam4.2145] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 01/27/2019] [Accepted: 03/18/2019] [Indexed: 12/18/2022] Open
Abstract
Pancreatic cancer (PC) has posed a great health threat to a growing number of people all over the world. Detection of serum miRNAs, being sensitive, noninvasive, and easy to obtain, has a great potential of being a novel screening method for PC patients. In this study, we investigated miRNA expression levels in serum by qRT-PCR. The study was divided into four phases: the screening, training, testing, and external validation stage. We firstly chose candidate miRNAs using Exiqon panels in the screening phase. Then, a total of 129 PC serum samples and 107 normal controls (NCs) were further analyzed in the following training and testing phases to identify differently expressed miRNAs. A cohort of 30 PC serum samples vs 30 NCs was used to confirm the diagnostic value of the identified miRNAs in the external validation phase. Moreover, miRNA expressions in additional 44 PC tumor tissue samples and the matched adjacent normal tissue samples as well as 32 pairs of serum-derived exosomes samples were also further explored. As a result, we identified six significantly upregulated miRNAs in the serum of PC: let-7b-5p, miR-192-5p, miR-19a-3p, miR-19b-3p, miR-223-3p, and miR-25-3p. A six-miRNA panel in serum was then established. The area under the receiver operating characteristic curves (AUC) for the panel was 0.910 for the combined training and testing phases, which showed higher diagnostic value than the individual miRNA. Prognostic value prediction using Cox's proportional hazards model and Kaplan-Meier curves showed that increased serum miR-19a-3p was closely related to worse overall survival (OS). In addition, significant upregulation of miR-192-5p, miR-19a-3p, and miR-19b-3p was observed in both PC tissue and serum-derived exosomes samples. In conclusion, we identified a six-miRNA (let-7b-5p, miR-192-5p, miR-19a-3p, miR-19b-3p, miR-223-3p, and miR-25-3p) panel in the serum for PC early and noninvasive diagnosis.
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Affiliation(s)
- Xuan Zou
- First Clinical College of Nanjing Medical University, Nanjing, PR China
| | - Jishu Wei
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
- Pancreas Institute, Nanjing Medical University, Nanjing, PR China
| | - Zebo Huang
- Department of Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, PR China
- Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Xin Zhou
- Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Zipeng Lu
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
- Pancreas Institute, Nanjing Medical University, Nanjing, PR China
| | - Wei Zhu
- Department of Oncology, The Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
- Department of Oncology, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, PR China
| | - Yi Miao
- Pancreas Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
- Pancreas Institute, Nanjing Medical University, Nanjing, PR China
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Abstract
Multiplex detection of biomolecules is important in bionanotechnology and clinical diagnostics. Multiplexing using engineered solutions such as microarrays, synthetic nanopores, and DNA barcodes is promising, but they require sophisticated design/engineering and typically yield semiquantitative information. Single-molecule fluorescence resonance energy transfer (smFRET) is an attractive tool in this regard as it enables both sensitive and quantitative detection. However, multiplexing with smFRET remains a great challenge as it requires either multiple excitation sources, an antenna system created by multiple FRET pairs, or multiple acceptors of the donor fluorophore, which complicates not only the labeling schemes but also data analysis, due to overlapping of FRET efficiencies ( EFRET). Here, we address these currently outstanding issues by designing interconvertible hairpin-based sensors (iHabSs) with nonoverlapping EFRET utilizing a single donor/acceptor pair and demonstrate a high-confidence multiplex detection of unlabeled nucleic acid sequences. We validated the reliability of our approach by systematically omitting one target at a time. Further, we demonstrate that these iHabSs are fully recyclable, sensitive with a limit of detection of ∼200 pM, and able to discriminate against single base mismatches. The multiplexed approach developed here has the potential to benefit the fields of biosensing and diagnostics by allowing simultaneous and quantitative detection of unlabeled nucleic acid biomarkers.
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Affiliation(s)
- Anisa Kaur
- Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, Virginia 23284, United States
| | - Kumar Sapkota
- Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, Virginia 23284, United States
| | - Soma Dhakal
- Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, Virginia 23284, United States
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Gajos-Michniewicz A, Czyz M. Role of miRNAs in Melanoma Metastasis. Cancers (Basel) 2019; 11:E326. [PMID: 30866509 PMCID: PMC6468614 DOI: 10.3390/cancers11030326] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 02/28/2019] [Accepted: 03/02/2019] [Indexed: 12/16/2022] Open
Abstract
Tumour metastasis is a multistep process. Melanoma is a highly aggressive cancer and metastasis accounts for the majority of patient deaths. microRNAs (miRNAs) are non-coding RNAs that affect the expression of their target genes. When aberrantly expressed they contribute to the development of melanoma. While miRNAs can act locally in the cell where they are synthesized, they can also influence the phenotype of neighboring melanoma cells or execute their function in the direct tumour microenvironment by modulating ECM (extracellular matrix) and the activity of fibroblasts, endothelial cells, and immune cells. miRNAs are involved in all stages of melanoma metastasis, including intravasation into the lumina of vessels, survival during circulation in cardiovascular or lymphatic systems, extravasation, and formation of the pre-metastatic niche in distant organs. miRNAs contribute to metabolic alterations that provide a selective advantage during melanoma progression. They play an important role in the development of drug resistance, including resistance to targeted therapies and immunotherapies. Distinct profiles of miRNA expression are detected at each step of melanoma development. Since miRNAs can be detected in liquid biopsies, they are considered biomarkers of early disease stages or response to treatment. This review summarizes recent findings regarding the role of miRNAs in melanoma metastasis.
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Affiliation(s)
- Anna Gajos-Michniewicz
- Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.
| | - Malgorzata Czyz
- Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.
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Gao W, Wong TS, Lv KX, Zhang MJ, Tsang RKY, Chan JYW. Detection of Epstein-Barr virus (EBV)-encoded microRNAs in plasma of patients with nasopharyngeal carcinoma. Head Neck 2018; 41:780-792. [PMID: 30548946 DOI: 10.1002/hed.25544] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 08/03/2018] [Accepted: 09/28/2018] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Nasopharyngeal carcinoma (NPC) latently infected by Epstein-Barr virus (EBV) expresses 40 EBV BART microRNAs (miRNAs). Difference in diagnostic efficacy of these miRNAs on NPC detection was observed. Here, we performed a comprehensive evaluation on the efficacy of these miRNAs. METHODS Quantitative polymerase chain reaction was performed on plasma nucleic acid isolated from patients with NPC and noncancer donors. RESULTS For primary NPC, BART2-5P, BART6-3P, BART7-3P, BART7-5P, BART9-5P, BART11-3P, BART17-5P, and BART19-5P were significantly elevated. For recurrent NPC, plasma levels of BART2-3P, BART2-5P, BART5-3P, BART5-5P, BART6-3P, BART8-3P, BART9-5P, BART17-5P, BART19-3P, and BART20-3P were significantly increased. Area under curve (AUC) analysis showed that BART19-5P had the best performance to identify NPC which was serologically EBV DNA undetectable. For recurrent NPC, BART8-3P and BART10-3P had highest AUC value for identifying cancer in EBV DNA undetectable plasma. CONCLUSION Our data supported the use of circulating EBV miRNAs in NPC and recurrent NPC detection.
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Affiliation(s)
- Wei Gao
- Division of Head and Neck, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.,Shenzhen Institute of Research and Innovation, The University of Hong Kong, China
| | - Thian-Sze Wong
- Division of Head and Neck, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.,Shenzhen Institute of Research and Innovation, The University of Hong Kong, China
| | - Ke-Xing Lv
- Division of Head and Neck, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Min-Juan Zhang
- Division of Head and Neck, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.,Shenzhen Institute of Research and Innovation, The University of Hong Kong, China
| | - Raymond King-Yin Tsang
- Division of Head and Neck, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.,Shenzhen Institute of Research and Innovation, The University of Hong Kong, China
| | - Jimmy Yu-Wai Chan
- Division of Head and Neck, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.,Shenzhen Institute of Research and Innovation, The University of Hong Kong, China
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MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis. Cells 2018; 7:cells7110219. [PMID: 30463376 PMCID: PMC6262636 DOI: 10.3390/cells7110219] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 11/15/2018] [Accepted: 11/17/2018] [Indexed: 12/30/2022] Open
Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable and fatal disorder characterized by the progressive loss of motor neurons in the cerebral cortex, brain stem, and spinal cord. Sporadic ALS form accounts for the majority of patients, but in 1–13.5% of cases the disease is inherited. The diagnosis of ALS is mainly based on clinical assessment and electrophysiological examinations with a history of symptom progression and is then made with a significant delay from symptom onset. Thus, the identification of biomarkers specific for ALS could be of a fundamental importance in the clinical practice. An ideal biomarker should display high specificity and sensitivity for discriminating ALS from control subjects and from ALS-mimics and other neurological diseases, and should then monitor disease progression within individual patients. microRNAs (miRNAs) are considered promising biomarkers for neurodegenerative diseases, since they are remarkably stable in human body fluids and can reflect physiological and pathological processes relevant for ALS. Here, we review the state of the art of miRNA biomarker identification for ALS in cerebrospinal fluid (CSF), blood and muscle tissue; we discuss advantages and disadvantages of different approaches, and underline the limits but also the great potential of this research for future practical applications.
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Wang XX, Ye FG, Zhang J, Li JJ, Chen QX, Lin PY, Song CG. Serum miR-4530 sensitizes breast cancer to neoadjuvant chemotherapy by suppressing RUNX2. Cancer Manag Res 2018; 10:4393-4400. [PMID: 30349372 PMCID: PMC6188109 DOI: 10.2147/cmar.s172205] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Purpose Neoadjuvant chemotherapy (NAC) plays a pivotal role in the treatment of locally advanced breast cancer (LABC); however, breast cancer is a heterogeneous disease, individual responses to chemotherapy are highly variable. Therefore, the purpose of the current research is to identify biomarkers that can predict the chemotherapeutic response. Patients and methods We recruited 78 patients with primary breast cancer who underwent taxane- and anthracycline-based NAC; these patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The microRNA microarray was conducted to explore differentially expressed miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) further validated the relationship between miR-4530 and chemosensitivity in breast cancer patients. Results No significant differences were observed between the two groups regarding the clinicopathological characteristics. miR-4530 showed the most potential involving breast cancer chemosensitivity. Mechanically, RUNX2 was identified one of the direct targets of miR-4530 and responsible for breast cancer chemosensitivity. Conclusion Our results revealed that elevated serum miR-4530 levels may sensitize breast cancer to taxane- and anthracycline-based NAC by suppressing RUNX2; therefore, this miRNA has the potential to be a new biomarker for predicting breast cancer chemosensitivity.
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Affiliation(s)
- Xiao-Xiao Wang
- Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China,
| | - Fu-Gui Ye
- Department of Breast Surgery, Key Laboratory of Breast Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
| | - Jie Zhang
- Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China,
| | - Jun-Jing Li
- Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China,
| | - Qing-Xia Chen
- Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China,
| | - Pei-Yang Lin
- Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China,
| | - Chuan-Gui Song
- Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China,
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Yang H, Zhang J, Li J, Zhao F, Shen Y, Xing X. Overexpression of miR-574-3p suppresses proliferation and induces apoptosis of chronic myeloid leukemia cells via targeting IL6/JAK/STAT3 pathway. Exp Ther Med 2018; 16:4296-4302. [PMID: 30344703 DOI: 10.3892/etm.2018.6700] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 08/23/2018] [Indexed: 12/16/2022] Open
Abstract
The present study aimed to elucidate the potential roles and regulatory mechanism of microRNA (miR)-574-3p in the development of chronic myeloid leukemia (CML). The expression of miR-574-3p in peripheral blood obtained from patients with CML was examined. Subsequently, miR-574-3p was overexpressed and suppressed in CML K562 cells to further investigate the effects of miR-574-3p on cell proliferation, and apoptosis. Furthermore, a luciferase reporter assay was performed to investigate whether interleukin-6 (IL-6) was a target of miR-574-3p. In addition, the regulatory association between miR-574-3p and the IL-6/Janus kinase (JNK)/signal transducer and activator of transcription-3 (STAT3) signaling pathway was explored. The expression of miR-574-3p in the peripheral blood obtained from patients with CML was significantly lower compared with that in healthy controls. Overexpression of miR-574-3p significantly inhibited the proliferation and induced the apoptosis of K562 cells, whereas suppression of miR-574-3p exhibited opposite effects. In addition, IL-6 was identified to be a direct target of miR-574-3p. Overexpression of IL-6 significantly promoted the proliferation and inhibited the apoptosis of K562 cells. Furthermore, overexpression of miR-574-3p inhibited the activation of the JAK/STAT3 signaling pathway, which was rescued by overexpression of IL-6. The results of the current study indicate that miR-574-3p overexpression may serve an important role in inhibiting proliferation and inducing apoptosis of K562 cells via suppression of IL-6/JAK/STAT3 signaling pathway activation. miR-574-3p may serve as a potential therapeutic target for CML.
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Affiliation(s)
- Haoying Yang
- Department of Blood Transfusion, San Er Ling Yi Hospital Affiliated to School of Medicine, Xi'an Jiaotong University, Hanzhong, Shanxi 723000, P.R. China
| | - Jun Zhang
- Department of Clinical Laboratory, San Er Ling Yi Hospital Affiliated to School of Medicine, Xi'an Jiaotong University, Hanzhong, Shanxi 723000, P.R. China
| | - Jiuping Li
- Department of Blood Transfusion, San Er Ling Yi Hospital Affiliated to School of Medicine, Xi'an Jiaotong University, Hanzhong, Shanxi 723000, P.R. China
| | - Furong Zhao
- Department of Blood Transfusion, San Er Ling Yi Hospital Affiliated to School of Medicine, Xi'an Jiaotong University, Hanzhong, Shanxi 723000, P.R. China
| | - Yao Shen
- Department of Clinical Laboratory, San Er Ling Yi Hospital Affiliated to School of Medicine, Xi'an Jiaotong University, Hanzhong, Shanxi 723000, P.R. China
| | - Xuemei Xing
- Department of Clinical Laboratory, San Er Ling Yi Hospital Affiliated to School of Medicine, Xi'an Jiaotong University, Hanzhong, Shanxi 723000, P.R. China
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Pedersen NJ, Jensen DH, Lelkaitis G, Kiss K, Charabi BW, Ullum H, Specht L, Schmidt AY, Nielsen FC, von Buchwald C. MicroRNA-based classifiers for diagnosis of oral cavity squamous cell carcinoma in tissue and plasma. Oral Oncol 2018; 83:46-52. [PMID: 30098778 DOI: 10.1016/j.oraloncology.2018.05.020] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 04/27/2018] [Accepted: 05/25/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND MicroRNAs (miRNAs) hold promise as diagnostic cancer biomarkers. Here we aimed to define the miRNome in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM), and to identify and validate new diagnostic miRNAs and miRNA combinations in formalin-fixed paraffin-embedded (FFPE) tissue samples and plasma samples. METHODS We performed next-generation miRNA sequencing in FFPE tissue samples of OSCC (n = 80) and NOM (n = 8). Our findings were validated by quantitative polymerase chain reaction (qPCR) analysis of OSCC (n = 195) and NOM (n = 103) FFPE tissue samples, and plasma samples from OSCC patients (n = 55) and healthy persons (n = 18). RESULTS The OSCC miRNome included 567 miRNAs, 66 of which were differentially expressed between OSCC and NOM. Using qPCR data, we constructed receiver operating curves to classify patients as NOM or OSCC based on miRNA combinations. The area under the curve was of 0.92 from FFPE tissue (miR-204-5p, miR-370, miR-1307, miR-193b-3p, and miR-144-5p), and 1.0 from plasma samples (miR-30a-5p and miR-769-5p). Model calibration and discrimination were evaluated using 10-fold cross-validation. CONCLUSIONS Analysis of the miRNome from many OSCC cases improves our knowledge of the importance of individual miRNAs and their predictive potential in OSCC. We successfully identified miRNA classifiers in FFPE OSCC tissue and plasma with a high discriminatory ability between OSCC and NOM. The proposed combination of miR-30a-5p and miR-769-5p in plasma from OSCC patients could serve as a minimal invasive biomarker for diagnosis and control of T-site recurrences.
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Affiliation(s)
- Nicklas Juel Pedersen
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - David Hebbelstrup Jensen
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Giedrius Lelkaitis
- Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Katalin Kiss
- Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Birgitte Wittenborg Charabi
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Henrik Ullum
- Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Lena Specht
- Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Ane Yde Schmidt
- Centre for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Finn Cilius Nielsen
- Centre for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Christian von Buchwald
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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Xu W, Zhou Y, Xu G, Geng B, Cui Q. Transcriptome analysis reveals non-identical microRNA profiles between arterial and venous plasma. Oncotarget 2018; 8:28471-28480. [PMID: 28212530 PMCID: PMC5438665 DOI: 10.18632/oncotarget.15310] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 01/24/2017] [Indexed: 12/27/2022] Open
Abstract
Circulating microRNAs presented in venous plasma have been demonstrated as powerful biomarkers for the complex diseases like cancer. Nevertheless, those presented in arterial plasma remained largely unexplored. Here, using microarray technique, we compared microRNA expression profiles of the matched arterial and venous plasma samples from the same male rats. Though the microRNA profiles were largely similar, we identified 24 differentially expressed microRNAs, including 10 arterial highly expressed microRNAs and 14 venous highly expressed microRNAs. The differentially expressed microRNAs were validated by qRT-PCR. Computational analysis of these microRNAs and their targets indicated that arterial highly expressed microRNAs were overrepresented for functional terms like hematopoiesis and diseases like Crohn's Disease and leukemia; while venous highly expressed microRNAs were enriched for cell differentiation function, and diseases like distal myopathies and heart failure. Our analysis also suggested significant correlations between plasma microRNA expression and tissue microRNA expression. Four arterial highly expressed microRNAs also showed enriched expression in specific tissues and would be novel biomarker candidates.
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Affiliation(s)
- Wenjing Xu
- Department of Physiology and Pathophysiology, Department of Biomedical Informatics, Centre for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Yuan Zhou
- Department of Physiology and Pathophysiology, Department of Biomedical Informatics, Centre for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Guoheng Xu
- Department of Physiology and Pathophysiology, Department of Biomedical Informatics, Centre for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Bin Geng
- Department of Physiology and Pathophysiology, Department of Biomedical Informatics, Centre for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
| | - Qinghua Cui
- Department of Physiology and Pathophysiology, Department of Biomedical Informatics, Centre for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
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45
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Li X, Lv Y, Hao J, Sun H, Gao N, Zhang C, Lu R, Wang S, Yin L, Pu Y, Chen R. Role of microRNA-4516 involved autophagy associated with exposure to fine particulate matter. Oncotarget 2018; 7:45385-45397. [PMID: 27329587 PMCID: PMC5216729 DOI: 10.18632/oncotarget.9978] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 05/23/2016] [Indexed: 12/22/2022] Open
Abstract
Metals are vital toxic components of fine particulate matter (PM2.5). Cellular responses to exposure to PM2.5 or PM metal components remain unknown. Post-transcriptional profiling and subsequent cell- and individual-based assays implied that the metal ion-binding miR-4516/RPL37/autophagy pathway could play a critical role in cellular responses to PM2.5 and PM metal stresses. miR-4516 was up-regulated in A549 cells exposed to PM2.5 and in the serum of individuals living in a city with moderate air pollution. The expression levels of the miR-4516 target genes, namely, RPL37 and UBA52, were involved in ribosome function and inhibited by exposure to PM2.5 and PM metal components. Autophagy in A549 cells was induced by PM2.5 exposure as a response to decreased RPL37 expression. Moreover, enhanced miR-4516 expression was positively correlated with the augmentation of the internal burden of aluminum and lead in individuals living in a city with moderate air pollution. Hereby, the miR-4516/RPL37/autophagy pathway may represent a novel mechanism that mediates responses to PM metal components.
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Affiliation(s)
- Xiaobo Li
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Yang Lv
- Department of Histology and Embryology, Hebei North University, Zhangjiakou 075000, China
| | - Jihong Hao
- Clinical Laboratory of The Second Hospital, Hebei Medical University, Shijiazhuang 050000, China
| | - Hao Sun
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Na Gao
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Chengcheng Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Runze Lu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Shizhi Wang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Lihong Yin
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Yuepu Pu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Rui Chen
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.,State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China
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46
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Zhang X, Ji W, Huang R, Li L, Wang X, Li L, Fu X, Sun Z, Li Z, Chen Q, Zhang M. MicroRNA-155 is a potential molecular marker of natural killer/T-cell lymphoma. Oncotarget 2018; 7:53808-53819. [PMID: 27462776 PMCID: PMC5288223 DOI: 10.18632/oncotarget.10780] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 07/09/2016] [Indexed: 12/22/2022] Open
Abstract
Natural killer/T-cell lymphoma (NKTCL) is characterized by its highly aggressive nature and rapid progression. MicroRNAs (miRNAs) play key roles in the development of NKTCL. We utilized next-generation Solexa high-throughput sequencing to compare miRNA expression in the SNK-6 and YTS NKTCL cell lines with expression in normal NK cells. We found that 195 miRNAs were upregulated in the SNK-6 cells and 286 miRNAs were upregulated in the YTS cells. Based on those results, we selected six miRNAs, including miRNA-155, and confirmed their expression using real-time polymerase chain reaction. Expression of miRNA-155 was higher in SNK-6 and YKS cells than in normal NK cells. We next determined the levels of miRNA-155 in the serum of healthy individuals and NKTCL patients, and correlated its expression with clinical parameters and inflammatory factors detected using enzyme-linked immunoabsorbent assays. Levels of miRNA-155 were higher in NKTCL patients' serum than in serum from healthy individuals. miRNA-155 expression was higher in patients with stable or progressive disease (SD+PD) than in those with partial or complete remission (PR+CR). While further studies are needed to clarify the underlying molecular mechanisms, it appears miRNA-155 may be a molecular marker of NKTCL.
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Affiliation(s)
- Xudong Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Weiguo Ji
- Department of Oncology, Third Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou 450008, China
| | - Ruixia Huang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Lifeng Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Xinhua Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Ling Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Xiaorui Fu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Zhenchang Sun
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Zhaoming Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Qingjiang Chen
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Mingzhi Zhang
- Department of Oncology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
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47
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Åkerman L, Casas R, Ludvigsson J, Tavira B, Skoglund C. Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in children with high risk for type 1 diabetes. PLoS One 2018; 13:e0191067. [PMID: 29346396 PMCID: PMC5773164 DOI: 10.1371/journal.pone.0191067] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 12/26/2017] [Indexed: 01/13/2023] Open
Abstract
Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability. Their expression in serum is altered in type 1 diabetes, but whether deviations exist in individuals with high risk for type 1 diabetes remains unexplored. We therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for multiple islet autoantibodies, age-matched healthy children (n = 17) and recent-onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR Panels from Exiqon. The miRNA levels in the high-risk group were similar to healthy controls, and no specific miRNA profile was identified for the high-risk group. However, serum miRNAs appeared to reflect glycemic status and ongoing islet autoimmunity in high-risk individuals, since several miRNAs were associated to glucose homeostasis and autoantibody titers. High-risk individuals progressing to clinical disease after the sampling could not be clearly distinguished from non-progressors, while miRNA expression in the type 1 diabetes group deviated significantly from high-risk individuals and healthy controls, perhaps explained by major metabolic disturbances around the time of diagnosis.
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Affiliation(s)
- Linda Åkerman
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
| | - Rosaura Casas
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
| | - Johnny Ludvigsson
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
- Crown Princess Victoria Children´s Hospital, University Hospital, Linköping, Region Östergötland, Sweden
| | - Beatriz Tavira
- Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
| | - Camilla Skoglund
- Division of Drug Research, Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
- * E-mail:
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48
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Feng R, Beeharry MK, Lu S, Sah BK, Yuan F, Yan M, Liu B, Li C, Zhu Z. Down-regulated serum miR-126 is associated with aggressive progression and poor prognosis of gastric cancer. Cancer Biomark 2018; 22:119-126. [PMID: 29562500 DOI: 10.3233/cbm-171099] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND miR-126 functions as a tumor suppressor in gastric cancer (GC), however, the clinical significance of serum miR-126 in GC remains unclear. OBJECTIVE To investigate the associations of serum miR-126 level with the clinicopathological characteristics and prognosis of GC patients. METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression levels of miR-126 in 338 GC patients' tissues and sera, and 50 healthy controls' sera. The associations of serum miR-126 with clinicopathological characteristics and clinical outcome were evaluated. RESULTS Compared with the matched adjacent non-tumor tissues and normal sera, miR-126 expression was significantly down-regulated in both tumor tissues and sera of GC patients. Importantly, there was a positive correlation between tissue and serum levels of miR-126 in GC patients. A reduced serum miR-126 level statistically correlated with aggressive clinicopathological characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. Notably, multivariate analysis identified reduced serum miR-126 level as an independent predictor for the unfavorable prognosis of GC. CONCLUSIONS These results indicate for the first time that serum miR-126 may serve as a novel prognostic biomarker in GC.
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Affiliation(s)
- Runhua Feng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Maneesh K Beeharry
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Sheng Lu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Birendra K Sah
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Fei Yuan
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Min Yan
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Bingya Liu
- Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Chen Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhenggang Zhu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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49
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Cruz-Gil S, Sanchez-Martinez R, Gomez de Cedron M, Martin-Hernandez R, Vargas T, Molina S, Herranz J, Davalos A, Reglero G, Ramirez de Molina A. Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role. J Lipid Res 2018; 59:14-24. [PMID: 29074607 PMCID: PMC5748493 DOI: 10.1194/jlr.m076752] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 10/05/2017] [Indexed: 02/06/2023] Open
Abstract
An abnormal acyl-CoA synthetase/stearoyl-CoA desaturase (ACSL/SCD) lipid network fuels colon cancer progression, endowing cells with invasive and migratory properties. Therapies against this metabolic network may be useful to improve clinical outcomes. Because micro-RNAs (miRNAs/miRs) are important epigenetic regulators, we investigated novel miRNAs targeting this pro-tumorigenic axis; hence to be used as therapeutic or prognostic miRNAs. Thirty-one putative common miRNAs were predicted to simultaneously target the three enzymes comprising the ACSL/SCD network. Target validation by quantitative RT-PCR, Western blotting, and luciferase assays showed miR-544a, miR-142, and miR-19b-1 as major regulators of the metabolic axis, ACSL/SCD Importantly, lower miR-19b-1 expression was associated with a decreased survival rate in colorectal cancer (CRC) patients, accordingly with ACSL/SCD involvement in patient relapse. Finally, miR-19b-1 regulated the pro-tumorigenic axis, ACSL/SCD, being able to inhibit invasion in colon cancer cells. Because its expression correlated with an increased survival rate in CRC patients, we propose miR-19b-1 as a potential noninvasive biomarker of disease-free survival and a promising therapeutic miRNA in CRC.
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Affiliation(s)
- Silvia Cruz-Gil
- Molecular Oncology and Nutritional Genomics of Cancer Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Ruth Sanchez-Martinez
- Molecular Oncology and Nutritional Genomics of Cancer Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Marta Gomez de Cedron
- Molecular Oncology and Nutritional Genomics of Cancer Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Roberto Martin-Hernandez
- Bioinformatics Unit, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Teodoro Vargas
- Molecular Oncology and Nutritional Genomics of Cancer Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Susana Molina
- Molecular Oncology and Nutritional Genomics of Cancer Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Jesús Herranz
- Biostatistics Unit, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Alberto Davalos
- Disorders of Lipid Metabolism and Molecular Nutrition Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Guillermo Reglero
- Molecular Oncology and Nutritional Genomics of Cancer Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
| | - Ana Ramirez de Molina
- Molecular Oncology and Nutritional Genomics of Cancer Group, Instituto Madrileño de Estudios Avanzados (IMDEA) Food Institute, CEI UAM+CSIC, Madrid, Spain
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50
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Sartorius K, Sartorius B, Kramvis A, Singh E, Turchinovich A, Burwinkel B, Madiba T, Winkler CA. Circulating microRNA's as a diagnostic tool for hepatocellular carcinoma in a hyper endemic HIV setting, KwaZulu-Natal, South Africa: a case control study protocol focusing on viral etiology. BMC Cancer 2017; 17:894. [PMID: 29282036 PMCID: PMC5745691 DOI: 10.1186/s12885-017-3915-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 12/14/2017] [Indexed: 12/15/2022] Open
Abstract
Background A wide range of studies has investigated the diagnostic proficiency of extracellular microRNAs (miRNAs) in hepatocellular cancer (HCC). HCC is expected to increase in Sub-Saharan Africa (SSA), due to endemic levels of viral infection (HBV/HIV), ageing and changing lifestyles. This unique aetiological background provides an opportunity for investigating potentially novel circulating miRNAs as biomarkers for HCC in a prospective study in South Africa. Methods This study will recruit HCC patients from two South African cancer hospitals, situated in Durban and Pietermaritzburg in the province of KwaZulu-Natal. These cases will include both HBV mono-infected and HBV/HIV co-infected HCC cases. The control group will consist of two (2) age and sex-matched healthy population controls per HCC case randomly selected from a Durban based laboratory. The controls will exclude patients if they have any evidence of chronic liver disease. A standardised reporting approach will be adopted to detect, quantify and normalize the level of circulating miRNAs in the blood sera of HCC cases and their controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) will be employed to quantity extracellular miRNAs. Differences in concentration of relevant miRNA by case/control status will be assessed using the Wilcoxon rank-sum (Mann-Whitney U) test. Adjustment for multiple testing (Bonferroni correction), receiver operating curves (ROC) and optimal breakpoint analyses will be employed to identify potential thresholds for the differentiation of miRNA levels of HCC cases and their controls. Discussion Although there is a growing base of literature regarding the role of circulating miRNAs as biomarkers, this promising field remains a ‘work in progress’. The aetiology of HBV infection in HCC is well understood, as well as it’s role in miRNA deregulation, however, the mediating role of HIV infection is unknown. HCC incidence in SSA, including South Africa, is expected to increase significantly in the next decade. A combination of factors, therefore, offers a unique opportunity to identify candidate circulating miRNAs as potential biomarkers for HBV/HIV infected HCC. Electronic supplementary material The online version of this article (10.1186/s12885-017-3915-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- K Sartorius
- Department of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, 4041, South Africa.,Faculty of Commerce, Law and Management, University of the Witwatersrand, Johannesburg, South Africa.,UKZN Gastrointestinal Cancer Research Centre (GICRC), Durban, South Africa
| | - B Sartorius
- Department of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, 4041, South Africa. .,UKZN Gastrointestinal Cancer Research Centre (GICRC), Durban, South Africa.
| | - A Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa
| | - E Singh
- South African National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa
| | - A Turchinovich
- Molecular Epidemiology Group, German Cancer Research Centre, Heidelberg, Germany.,SciBerg e.Kfm, Mannheim, Germany
| | - B Burwinkel
- Molecular Epidemiology Group, German Cancer Research Centre, Heidelberg, Germany
| | - T Madiba
- UKZN Gastrointestinal Cancer Research Centre (GICRC), Durban, South Africa
| | - C A Winkler
- Basic Research Laboratory, Centre for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Inc. Frederick Nat. Lab. for Cancer Research, Frederick, MD, USA
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