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Zhang Y, Yue NN, Chen LY, Tian CM, Yao J, Wang LS, Liang YJ, Wei DR, Ma HL, Li DF. Exosomal biomarkers: A novel frontier in the diagnosis of gastrointestinal cancers. World J Gastrointest Oncol 2025; 17:103591. [DOI: 10.4251/wjgo.v17.i4.103591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/24/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
Gastrointestinal (GI) cancers, which predominantly manifest in the stomach, colorectum, liver, esophagus, and pancreas, accounting for approximately 35% of global cancer-related mortality. The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers. This non-invasive technique not only facilitates prompt therapeutic intervention, but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence. The wealth of circulating exosomes present in body fluids is often enriched with proteins, lipids, microRNAs, and other RNAs derived from tumor cells. These specific cargo components are reflective of processes involved in GI tumorigenesis, tumor progression, and response to treatment. As such, they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer. In this review, we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles. We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application. Furthermore, we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.
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Affiliation(s)
- Yuan Zhang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
- Department of Medical Administration, Huizhou Institute for Occupational Health, Huizhou 516000, Guangdong Province, China
| | - Ning-Ning Yue
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), Shenzhen 518000, Guangdong Province, China
| | - Li-Yu Chen
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People’s Hospital (Jinan University of Second Clinical Medical Sciences), Shenzhen 518000, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen 518000, Guangdong Province, China
| | - Dao-Ru Wei
- Department of Rehabilitation, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Hua-Lin Ma
- Department of Nephrology, The Second Clinical Medical College, Jinan University, Shenzhen 518020, Guangdong Province, China
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
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Karaca Dogan B, Salman Yilmaz S, Izgi GN, Ozen M. Circulating non-coding RNAs as a tool for liquid biopsy in solid tumors. Epigenomics 2025; 17:335-358. [PMID: 40040488 DOI: 10.1080/17501911.2025.2467021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 02/10/2025] [Indexed: 03/06/2025] Open
Abstract
Solid tumors are significant causes of global mortality and morbidity. Recent research has primarily concentrated on finding pathology-specific molecules that can be acquired non-invasively and that can change as the disease progresses or in response to treatment. The focus of research has moved to RNA molecules that are either freely circulating in body fluids or bundled in microvesicles and exosomes because of their great stability in challenging environments, ease of accessibility, and changes in level in response to therapy. In this context, there are many non-coding RNAs that can be used for this purpose in liquid biopsies. Out of these, microRNAs have been extensively studied. However, there has been an increase of interest in studying long non-coding RNAs, piwi interacting RNAs, circular RNAs, and other small non-coding RNAs. In this article, an overview of the most researched circulating non-coding RNAs in solid tumors will be reviewed, along with a discussion of the significance of these molecules for early diagnosis, prognosis, and therapeutic targets. The publications analyzed were extracted from the PubMed database between 2008 and June 2024.
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Affiliation(s)
- Beyza Karaca Dogan
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Seda Salman Yilmaz
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Medical Services and Techniques Medical Monitoring Techniques Pr. Vocational School of Health Services, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Gizem Nur Izgi
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Mustafa Ozen
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
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Alhajlah S, Jasim SA, Altalbawy FMA, Bansal P, Kaur H, Mohammed JS, Fenjan MN, Edan RT, Sharma MK, Zwamel AH. Exploring the role of exosomal lncRNA in cancer immunopathogenesis: Unraveling the immune response and EMT pathways. Exp Cell Res 2025; 445:114401. [PMID: 39740727 DOI: 10.1016/j.yexcr.2024.114401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/26/2024] [Accepted: 12/28/2024] [Indexed: 01/02/2025]
Abstract
Exosomes are membrane-bound vesicles secreted by diverse cell types, serving as crucial mediators in intercellular communication and significantly influencing cancer development. Exosomes facilitate complex signaling processes in the tumor microenvironment for immunomodulation, metastasis, angiogenesis, and treatment resistance. Notably, long non-coding RNAs (lncRNAs), a class of non-coding RNAs, engage with mRNA, DNA, proteins, and miRNAs to modulate gene expression through multiple mechanisms, including transcriptional, post-transcriptional, translational, and epigenetic pathways. The quantitative dynamics of exosomal lncRNAs show a consistent variation correlating with cancer progression and metastasis, suggesting their potential utility as biomarkers for cancer diagnosis and prognosis. Additionally, exosomal lncRNAs can yield critical insights into therapeutic responses in patients. The identification of exosomal lncRNAs as indicators for various cancer subtypes presents them not only as prognostic tools but also as promising therapeutic targets. Despite their potential, the precise functions of exosomal lncRNAs in the cancer biology landscape remain inadequately understood. This paper delves into the multifaceted roles of exosomal lncRNAs, particularly in the context of breast cancer, highlighting their promise for therapeutic applications. A thorough comprehension of exosomal lncRNAs is imperative for advancing our knowledge of the underlying mechanisms of breast cancer, ultimately paving the way for the development of more effective treatment strategies for patients.
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Affiliation(s)
- Sharif Alhajlah
- Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra, 11961, Saudi Arabia.
| | - Saade Abdalkareem Jasim
- Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-maarif, Anbar, Iraq.
| | - Farag M A Altalbawy
- Department of Chemistry, University College of Duba, University of Tabuk, Tabuk, 71911, Saudi Arabia; National Institute of Laser Enhanced Sciences (NILES), University of Cairo, Giza, 12613, Egypt.
| | - Pooja Bansal
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka, 560069, India; Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India.
| | - Harpreet Kaur
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh, 247341, India; Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand, 831001, India.
| | - Jaafaru Sani Mohammed
- Medical Analysis Department, Faculty of Applied Science, Tishk International University, Erbil, Iraq.
| | - Mohammed N Fenjan
- College of Health and Medical Technology, Al-Ayen University, Thi-Qar, Iraq.
| | - Reem Turki Edan
- Department of Medical Laboratories Technology, AL-Nisour University College, Baghdad, Iraq.
| | - M K Sharma
- Chaudhary Charan Singh University Meerut, Uttar Pradesh, India.
| | - Ahmed Hussein Zwamel
- Medical Laboratory Technique College, The Islamic University, Najaf, Iraq; Medical Laboratory Technique College, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq; Medical Laboratory Technique College, The Islamic University of Babylon, Babylon, Iraq.
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Huang C, Li J, Xie Z, Hu X, Huang Y. Relationship between exosomes and cancer: formation, diagnosis, and treatment. Int J Biol Sci 2025; 21:40-62. [PMID: 39744442 PMCID: PMC11667803 DOI: 10.7150/ijbs.95763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 11/02/2024] [Indexed: 01/11/2025] Open
Abstract
Exosomes are a member of extracellular vesicles. However, their biological characteristics differ from those of other vesicles, and recently, their powerful functions as information molecules, biomarkers, and carriers have been demonstrated. Malignancies are the leading cause of high morbidity and mortality worldwide. The cure rate of malignancies can be improved by improving early screening rates and therapy. Moreover, a close correlation between exosomes and malignancies has been observed. An in-depth study of exosomes can provide new methods for diagnosing and treating tumors. Therefore, this study aimed to review, sort, and summarize such achievements, and present ideas and opinions on the application of exosomes in tumor treatment.
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Affiliation(s)
- Chen Huang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jiajin Li
- Sichuan university, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Zichuan Xie
- Sichuan university, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Xiangjun Hu
- Sichuan university, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yan Huang
- Health Management Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China
- State Key Laboratory of Respiratory Health and Multimorbidity, China
- Research Laboratory for Prediction and Evaluation of Chronic Diseases in the Elderly, National Clinical Research Center for Geriatric Diseases, China
- General Practice Research Institute, West China Hospital, Sichuan University, Chengdu, China
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Wang Z, Xie C, Chen X. Diagnostic and therapeutic role of non-coding RNAs regulating programmed cell death in melanoma. Front Oncol 2024; 14:1476684. [PMID: 39777348 PMCID: PMC11703721 DOI: 10.3389/fonc.2024.1476684] [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: 08/06/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
lncRNAs (long non-coding RNAs) are heterogeneous RNA molecules that modulate various cellular processes, such as proliferation, differentiation, migration, invasion, and apoptosis, via different mechanisms. An increasing amount of research indicates that abnormal expression of lncRNA influences the development of drug resistance as well as the genesis and advancement of cancer, including melanoma. Furthermore, they are attractive biomarkers for non-invasive cancer diagnostics due to their strongly modulated expression and improved tissue and disease specificity. This review offers a succinct overview of the present understanding concerning the potential diagnostic biomarker potential of lncRNAs in melanoma. Cell death occurs frequently during growth and throughout life and is an active, organized, and genetically determined process. It is essential for the regulation of homeostasis. Controlled cell death and non-programmed cell death are both forms of cell death. The most prevalent forms of regulatory cell death are pyroptosis, ferroptosis, autophagy, necroptosis, necrosis, and apoptosis. Ferroptosis, pyroptosis, and autophagy are less common forms of cell death compared to necrosis, apoptosis, and necroptosis. ncRNAs are regulatory RNA molecules that are not involved in encoding proteins. They primarily consist of circular RNAs (circ RNAs), lncRNAs, and microRNAs (miRNAs). Moreover, non-coding RNAs have the ability to modulate tumor cell autophagy, pyroptosis, and ferroptosis at the transcriptional or post-transcriptional stage, as well as function as oncogenes and tumor suppressor genes, which can have considerable effects on the incidence and growth of tumors. This review concentrated on the recent advancements in the research of the diagnostic and therapeutic functions of ncRNAs in the regulation of programmed cell death in melanoma.
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Affiliation(s)
- Zixu Wang
- Office for Doctoral Studies, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Cong Xie
- Office for Doctoral Studies, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Xiao Chen
- Office for Postgraduate Student Studies, Kunming Medical University, Kunming, China
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Jiang X, Qu A, Zhang S, Jin S, Wang L, Zhang Y. RNA-seq profiling identified a three-lncRNA panel in serum as potential biomarker for muscle-invasive bladder cancer. Front Oncol 2024; 14:1451009. [PMID: 39737397 PMCID: PMC11683095 DOI: 10.3389/fonc.2024.1451009] [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: 06/18/2024] [Accepted: 12/02/2024] [Indexed: 01/01/2025] Open
Abstract
Background Preoperative determination of muscular infiltration is crucial for appropriate treatment planning in patients with muscle-invasive bladder cancer (MIBC). We aimed to explore early diagnostic biomarkers in serum for MIBC in this study. Methods The expression profiles of long noncoding RNA (lncRNA) were initially screened by high-throughput sequencing and evaluation of potential lncRNAs were conducted by two phases of RT-qPCR assays using serum samples from 190 patients with MIBC and 190 non-muscle-invasive BC (NMIBC) patients. Multivariate logistic regression analysis was applied to establish a diagnostic signature with high accuracy and Fagan's nomogram was plotted to promote clinical application. Bioinformatics analysis was used to determine the potential miRNA-mRNA binding of candidate lncRNAs. Results We identified three differentially expressed lncRNAs (LINC00565, LINC00592 and NDUFA6-AS1) and established a 3-lncRNA panel which demonstrated high diagnostic accuracy for MIBC with an AUC of 0.903 (95% CI: 0.850-0.942) and 0.875 (95% CI: 0.802-0.928) in the training and validation set. Moreover, construction and assessment of Fagan'nomogram demonstrated that the 3-lncRNA panel could exhibit practical and helpful values for clinical use. Finally, a network map based on LINC00565 was constructed and we found that the expression of miR-143-5p and miR-4516 were significantly correlated with LINC00565 in MIBC. Conclusion Our findings indicated that the constructed 3-lncRNA panel in serum showed favorable diagnostic capacity and might serve as promising non-invasive biomarkers in the early diagnosis of MIBC.
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Affiliation(s)
- Xiumei Jiang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Ailin Qu
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Shoucai Zhang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Shuchao Jin
- Department of Urology, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Lishui Wang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, China
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Wang C, Shi ZZ. Exosomes in esophageal cancer: function and therapeutic prospects. Med Oncol 2024; 42:18. [PMID: 39601925 DOI: 10.1007/s12032-024-02543-x] [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: 08/05/2024] [Accepted: 10/15/2024] [Indexed: 11/29/2024]
Abstract
Esophageal cancer (EC) is one of the most common malignant tumors worldwide. Exosomes are a type of extracellular vesicles produced by eukaryotic cells and present in all body fluids. Recent studies have revealed that exosomes can be used as a tool for cell signaling and have great potential in cancer diagnosis and treatment strategies. This article reviews the research progress of exosomes in EC in recent years, mainly including the mechanism of action, diagnostic markers, therapeutic targets, and drug carriers. The challenges faced are discussed to provide guidelines for further research in future.
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Affiliation(s)
- Chong Wang
- Medical School, Kunming University of Science and Technology, Kunming, 650500, China
| | - Zhi-Zhou Shi
- Medical School, Kunming University of Science and Technology, Kunming, 650500, China.
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Chang J, Zhang L, Li Z, Qian C, Du J. Exosomal non-coding RNAs (ncRNAs) as potential biomarkers in tumor early diagnosis. Biochim Biophys Acta Rev Cancer 2024; 1879:189188. [PMID: 39313040 DOI: 10.1016/j.bbcan.2024.189188] [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: 06/13/2024] [Revised: 09/19/2024] [Accepted: 09/19/2024] [Indexed: 09/25/2024]
Abstract
Exosomes, extracellular vesicles carrying a cargo rich in various non-coding RNAs (ncRNAs), have emerged as crucial mediators of intercellular communication. Their stability, abundance, and specificity make exosomal ncRNAs promising candidates for biomarker discovery. The discovery of exosomal ncRNAs has unveiled a novel avenue for the exploration of biomarkers in tumor early diagnosis. This review consolidates current knowledge on the role of exosomal ncRNAs as potential biomarkers in the early detection of various tumors. We provide an overview of recent studies demonstrating the diagnostic potential of exosomal ncRNAs across multiple cancer types, highlighting their sensitivity, specificity, and feasibility for early detection. This review underscores the potential of exosomal ncRNAs as non-invasive biomarkers for early tumor diagnosis, paving the way for improved clinical outcomes through timely intervention and personalized management strategies.
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Affiliation(s)
- Jingyue Chang
- School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China
| | - Lingquan Zhang
- School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China
| | - Zeting Li
- School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China
| | - Chungen Qian
- Department of Reagent Research and Development, Shenzhen YHLO Biotech Co., Ltd., Shenzhen 518172, Guangdong, China.
| | - Juan Du
- School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China; The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China.
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Yuan L, Ji H, Cao Y, Yi H, Leng Q, Zhou J, Mei X. Exosomes in esophageal cancer: Promising nanocarriers in cancer progression, diagnosis, prognosis, and therapy. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1989. [PMID: 39217461 DOI: 10.1002/wnan.1989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 06/26/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024]
Abstract
Esophageal cancer (EC) is one of the most fatal cancers all over the world. Sensitive detection modalities for early-stage EC and efficient treatment methods are urgently needed for the improvement of the prognosis of EC. Exosomes are small vesicles for intercellular communication, mediating many biological responses including cancer progression, which are not only promising biomarkers for diagnosis and prognosis but also therapeutic tools for EC. This review provides an overview of the relationships between exosomes and EC progression, as well as the application of exosomes in the diagnosis, prognosis, and treatment of EC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
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Affiliation(s)
- Ligong Yuan
- Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Haoran Ji
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yang Cao
- Peking University Health Science Center, Peking University, Beijing, China
| | - Hang Yi
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qihao Leng
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Jie Zhou
- Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California, USA
| | - Xinyu Mei
- Department of Thoracic Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
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Marima R, Basera A, Miya T, Damane BP, Kandhavelu J, Mirza S, Penny C, Dlamini Z. Exosomal long non-coding RNAs in cancer: Interplay, modulation, and therapeutic avenues. Noncoding RNA Res 2024; 9:887-900. [PMID: 38616862 PMCID: PMC11015109 DOI: 10.1016/j.ncrna.2024.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/20/2024] [Accepted: 03/29/2024] [Indexed: 04/16/2024] Open
Abstract
In the intricate field of cancer biology, researchers are increasingly intrigued by the emerging role of exosomal long non-coding RNAs (lncRNAs) due to their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. These exosomal lncRNAs, carried within extracellular vesicles, play a vital partin tumorigenesis and disease progression by facilitating communication networks between tumor cells and their local microenvironment, making them an ideal candidates for use in a liquid biopsy approach. However, exosomal lncRNAs remain an understudied area, especially in cancer biology. Therefore this review aims to comprehensively explore the dynamic interplay between exosomal lncRNAs and various cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs in these processes can potentially unveil novel diagnostic markers and therapeutic targets for cancer. Additionally, the emergence of RNA-based therapeutics presents exciting opportunities for targeting exosomal lncRNAs, offering innovative strategies to combat cancer progression and improve treatment outcomes. Thus, this review provides insights into the current understanding of exosomal lncRNAs in cancer biology, highlighting their crucial roles, regulatory mechanisms, and the evolving landscape of therapeutic interventions. Furthermore, we have also discussed the advantage of exosomes as therapeutic carriers of lncRNAs for the development of personalized targeted therapy for cancer patients.
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Affiliation(s)
- Rahaba Marima
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChi Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, South Africa
| | - Afra Basera
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChi Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, South Africa
- Department of Medical Oncology, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, South Africa
| | - Thabiso Miya
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChi Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, South Africa
| | - Botle Precious Damane
- Department of Surgery, Steve Biko Academic Hospital, University of Pretoria, Pretoria, 0028, South Africa
| | - Jeyalakshmi Kandhavelu
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA
| | - Sheefa Mirza
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Parktown, 2193, South Africa
| | - Clement Penny
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Parktown, 2193, South Africa
| | - Zodwa Dlamini
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChi Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, South Africa
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11
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Sun S, Shao Y, Gu W. The roles of exosomes in esophageal cancer. Discov Oncol 2024; 15:371. [PMID: 39190048 DOI: 10.1007/s12672-024-01259-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 08/21/2024] [Indexed: 08/28/2024] Open
Abstract
The incidence and mortality rate of esophageal cancer (EC) are higher worldwide. Exosomes are nanoscale vesicles derived from various types of cells, exhibiting a stable presence in bodily fluids, and contain a plethora of bioactive components including proteins, DNA, and RNA. Exosomes can mediate cell-to-cell communication and signaling. Numerous studies conducted both domestically and internationally have indicated the significant involvement of exosomes in tumor development and their potential as novel diagnostic and prognostic biomarkers for liquid biopsy. This review seeks to consolidate the role of exosomes and bioactive substances in the progression of EC and elaborate on the opportunities and challenges associated with the clinical application of exosomes in EC.
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Affiliation(s)
- Shihong Sun
- Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, China
| | - Yingjie Shao
- Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, China.
| | - Wendong Gu
- Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou, 213003, China.
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Hao MJ, Cheng ZY, Gao Y, Xin L, Yu CT, Wang TL, Li ZS, Wang LW. Liquid biopsy of oesophageal squamous cell carcinoma: implications in diagnosis, prognosis, and treatment monitoring. Scand J Gastroenterol 2024; 59:698-709. [PMID: 38466190 DOI: 10.1080/00365521.2024.2310167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 01/18/2024] [Accepted: 01/20/2024] [Indexed: 03/12/2024]
Abstract
Oesophageal squamous cell carcinoma (ESCC) is a common malignant tumour of the gastrointestinal tract. Early detection and access to appropriate treatment are crucial for the long-term survival of patients. However, limited diagnostic and monitoring methods are available for identifying early stage ESCC. Endoscopic screening and surgical resection are commonly used to diagnose and treat early ESCC. However, these methods have disadvantages, such as high recurrence, lethality, and mortality rates. Therefore, methods to improve early diagnosis of ESCC and reduce its mortality rate are urgently required. In 1961, Gary et al. proposed a novel liquid biopsy approach for clinical diagnosis. This involved examining exosomes, circulating tumour cells, circulating free DNA, and circulating free RNA in body fluids. The ability of liquid biopsy to obtain samples repeatedly, wide detection range, and fast detection speed make it a feasible option for non-invasive tumour detection. In clinical practice, liquid biopsy technology has gained popularity for early screening, diagnosis, treatment efficacy monitoring, and prognosis assessment. Thus, this is a highly promising examination method. However, there have been no comprehensive reviews on the four factors of liquid biopsy in the context of ESCC. This review aimed to analyse the progress of liquid biopsy research for ESCC, including its classification, components, and potential future applications.
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Affiliation(s)
- Mei-Juan Hao
- University of Shanghai for Science and Technology, Shanghai, China
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
- Department of Anaesthesia and Surgery, Guiyang Fourth People's Hospital, Guiyang, China
| | - Zhi-Yuan Cheng
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ye Gao
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Lei Xin
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Chu-Ting Yu
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Ting-Lu Wang
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Luo-Wei Wang
- Department of Gastroenterology, The First Affiliated Hospital of Naval Medical University, Shanghai, China
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13
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Saikia S, Postwala H, Athilingam VP, Anandan A, Padma VV, Kalita PP, Chorawala M, Prajapati B. Single Nucleotide Polymorphisms (SNPs) in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer. Curr Pharm Biotechnol 2024; 25:1915-1938. [PMID: 38310451 DOI: 10.2174/0113892010265004231116092802] [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: 07/14/2023] [Revised: 10/02/2023] [Accepted: 10/04/2023] [Indexed: 02/05/2024]
Abstract
Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma (ESCC). These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci (eQTL) have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.
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Affiliation(s)
- Surovi Saikia
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - Humzah Postwala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, India
| | - Vishnu Prabhu Athilingam
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - Aparna Anandan
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - V Vijaya Padma
- Department of Natural Product Chemistry, Translational Research Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu, India
| | - Partha P Kalita
- Program of Biotechnology, Assam Down Town University, Panikhaiti, Guwahati 781026, Assam, India
| | - Mehul Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Ahmedabad, India
| | - Bhupendra Prajapati
- Department of Pharmaceutics and Pharmaceutical Technology, Shree. S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India
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14
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Ning XY, Ma JH, He W, Ma JT. Role of exosomes in metastasis and therapeutic resistance in esophageal cancer. World J Gastroenterol 2023; 29:5699-5715. [PMID: 38075847 PMCID: PMC10701334 DOI: 10.3748/wjg.v29.i42.5699] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 09/13/2023] [Accepted: 11/08/2023] [Indexed: 11/13/2023] Open
Abstract
Esophageal cancer (EC) has a high incidence and mortality rate and is emerging as one of the most common health problems globally. Owing to the lack of sensitive detection methods, uncontrollable rapid metastasis, and pervasive treatment resistance, EC is often diagnosed in advanced stages and is susceptible to local recurrence. Exosomes are important components of intercellular communication and the exosome-mediated crosstalk between the cancer and surrounding cells within the tumor microenvironment plays a crucial role in the metastasis, progression, and therapeutic resistance of EC. Considering the critical role of exosomes in tumor pathogenesis, this review focused on elucidating the impact of exosomes on EC metastasis and therapeutic resistance. Here, we summarized the relevant signaling pathways involved in these processes. In addition, we discussed the potential clinical applications of exosomes for the early diagnosis, prognosis, and treatment of EC.
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Affiliation(s)
- Xing-Yu Ning
- The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Jin-Hu Ma
- The Second School of Clinical Medicine, Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Wei He
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
| | - Jun-Ting Ma
- School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui Province, China
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15
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Xi Y, Shen Y, Chen L, Tan L, Shen W, Niu X. Exosome-mediated metabolic reprogramming: Implications in esophageal carcinoma progression and tumor microenvironment remodeling. Cytokine Growth Factor Rev 2023; 73:78-92. [PMID: 37696716 DOI: 10.1016/j.cytogfr.2023.08.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Accepted: 08/28/2023] [Indexed: 09/13/2023]
Abstract
Esophageal carcinoma is among the most fatal malignancies with increasing incidence globally. Tumor onset and progression can be driven by metabolic reprogramming, especially during esophageal carcinoma development. Exosomes, a subset of extracellular vesicles, display an average size of ∼100 nanometers, containing multifarious components (nucleic acids, proteins, lipids, etc.). An increasing number of studies have shown that exosomes are capable of transferring molecules with biological functions into recipient cells, which play crucial roles in esophageal carcinoma progression and tumor microenvironment that is a highly heterogeneous ecosystem through rewriting the metabolic processes in tumor cells and environmental stromal cells. The review introduces the reprogramming of glucose, lipid, amino acid, mitochondrial metabolism in esophageal carcinoma, and summarize current pharmaceutical agents targeting such aberrant metabolism rewiring. We also comprehensively overview the biogenesis and release of exosomes, and recent advances of exosomal cargoes and functions in esophageal carcinoma and their promising clinical application. Moreover, we discuss how exosomes trigger tumor growth, metastasis, drug resistance, and immunosuppression as well as tumor microenvironment remodeling through focusing on their capacity to transfer materials between cells or between cells and tissues and modulate metabolic reprogramming, thus providing a theoretical reference for the design potential pharmaceutical agents targeting these mechanisms. Altogether, our review attempts to fully understand the significance of exosome-based metabolic rewriting in esophageal carcinoma progression and remodeling of the tumor microenvironment, bringing novel insights into the prevention and treatment of esophageal carcinoma in the future.
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Affiliation(s)
- Yong Xi
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo 315040, Zhejiang, China; Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China
| | - Yaxing Shen
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Lijie Chen
- School of Medicine, Xiamen University, Xiamen 361102, Fujian, China; China Medical University, Shenyang 110122, Liaoning, China
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Weiyu Shen
- Department of Thoracic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo 315040, Zhejiang, China.
| | - Xing Niu
- China Medical University, Shenyang 110122, Liaoning, China.
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16
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Si MY, Rao DY, Xia Y, Sang CP, Mao KY, Liu XJ, Zhang ZX, Tang ZX. Role of exosomal noncoding RNA in esophageal carcinoma. Front Oncol 2023; 13:1126890. [PMID: 37234976 PMCID: PMC10206631 DOI: 10.3389/fonc.2023.1126890] [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: 12/18/2022] [Accepted: 03/31/2023] [Indexed: 05/28/2023] Open
Abstract
Esophageal cancer is a common malignant tumor with a high degree of malignancy. Understanding its pathogenesis and identifying early diagnostic biomarkers can significantly improve the prognosis of esophageal cancer patients. Exosomes are small double-membrane vesicles found in various body fluids containing various components (DNA, RNA, and proteins) that mediate intercellular signal communication. Non-coding RNAs are a class of gene transcription products that encode polypeptide functions and are widely detected in exosomes. There is growing evidence that exosomal non-coding RNAs are involved in cancer growth, metastasis and angiogenesis, and can also be used as diagnostic and prognostic markers. This article reviews the recent progress in exosomal non-coding RNAs in esophageal cancer, including research progress, diagnostic value, proliferation, migration, invasion, and drug resistance, provide new ideas for the precise treatment of esophageal cancer.
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Affiliation(s)
- Mao-Yan Si
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Ding-Yu Rao
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Yao Xia
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Cheng-Peng Sang
- Department of Cardiothoracic Surgery, The Affiliated Huaian Hospital of Xuzhou Medical University, Huai’an, Jiangsu, China
| | - Kai-Yun Mao
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Xiang-Jin Liu
- First Clinical Medical College, Gannan Medical University, Ganzhou, China
| | - Zu-Xiong Zhang
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Zhi-Xian Tang
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
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17
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Vosough P, Khatami SH, Hashemloo A, Tajbakhsh A, Karimi-Fard F, Taghvimi S, Taheri-Anganeh M, Soltani Fard E, Savardashtaki A, Movahedpour A. Exosomal lncRNAs in gastrointestinal cancer. Clin Chim Acta 2023; 540:117216. [PMID: 36592922 DOI: 10.1016/j.cca.2022.117216] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 12/24/2022] [Accepted: 12/29/2022] [Indexed: 01/01/2023]
Abstract
Gastrointestinal cancer (GIC) remains a leading cause of morbidity and mortality worldwide. Unfortunately, these cancers are diagnosed in advanced metastatic stages due to lack of reliable biomarkers that are sufficiently specific and sensitive in early disease. There has been growing evidence that circulating exosomes can be used to diagnose cancer non-invasively with limited risks and side effects. Furthermore, exosomal long non-coding RNAs (lncRNAs) are emerging as a new class of promising biomarkers in cancer. This review provides an overview of the extraction and detection of exosomal lncRNAs with a focus on their potential role in GIC.
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Affiliation(s)
- Parisa Vosough
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyyed Hossein Khatami
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Sina Taghvimi
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Elahe Soltani Fard
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
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18
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Zhao L, Yu L, Wang X, He J, Zhu X, Zhang R, Yang A. Mechanisms of function and clinical potential of exosomes in esophageal squamous cell carcinoma. Cancer Lett 2023; 553:215993. [PMID: 36328162 DOI: 10.1016/j.canlet.2022.215993] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/05/2022] [Accepted: 10/27/2022] [Indexed: 11/20/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal and widespread malignancies in China. Exosomes, a subset of tiny extracellular vesicles manufactured by all cells and present in all body fluids, contribute to intercellular communication and have become a focus of the search for new therapeutic strategies for cancer. A number of global analyses of exosome-mediated functions and regulatory mechanism in malignant diseases have recently been reported. There is extensive evidence that exosomes can be used as diagnostic and prognostic markers for cancer. However, our understanding of their clinical value and mechanisms of action in ESCC is still limited and has not been systematically reviewed. Here, we review current research specifically focused on the functions and mechanisms of action of ESCC tumor-derived exosomes and non-ESCC-derived exosomes in ESCC progression and describe opportunities and challenges in the clinical translation of exosomes.
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Affiliation(s)
- Lijun Zhao
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Lili Yu
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Xiangpeng Wang
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Jangtao He
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China
| | - Xiaofei Zhu
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
| | - Rui Zhang
- The State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.
| | - Angang Yang
- Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan, China; The State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.
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19
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Extracellular Vesicles Are Important Mediators That Regulate Tumor Lymph Node Metastasis via the Immune System. Int J Mol Sci 2023; 24:ijms24021362. [PMID: 36674900 PMCID: PMC9865533 DOI: 10.3390/ijms24021362] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/27/2022] [Accepted: 01/05/2023] [Indexed: 01/13/2023] Open
Abstract
Extracellular vesicles (EVs) are particles with a lipid bilayer structure, and they are secreted by various cells in the body. EVs interact with and modulate the biological functions of recipient cells by transporting their cargoes, such as nucleic acids and proteins. EVs influence various biological phenomena, including disease progression. They also participate in tumor progression by stimulating a variety of signaling pathways and regulating immune system activation. EVs induce immune tolerance by suppressing CD8+ T-cell activation or polarizing macrophages toward the M2 phenotype, which results in tumor cell proliferation, migration, invasion, and metastasis. Moreover, immune checkpoint molecules are also expressed on the surface of EVs that are secreted by tumors that express these molecules, allowing tumor cells to not only evade immune cell attack but also acquire resistance to immune checkpoint inhibitors. During tumor metastasis, EVs contribute to microenvironmental changes in distant organs before metastatic lesions appear; thus, EVs establish a premetastatic niche. In particular, lymph nodes are adjacent organs that are connected to tumor lesions via lymph vessels, so that tumor cells metastasize to draining lymph nodes at first, such as sentinel lymph nodes. When EVs influence the microenvironment of lymph nodes, which are secondary lymphoid tissues, the immune response against tumor cells is weakened; subsequently, tumor cells spread throughout the body. In this review, we will discuss the association between EVs and tumor progression via the immune system as well as the clinical application of EVs as biomarkers and therapeutic agents.
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20
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Badowski C, He B, Garmire LX. Blood-derived lncRNAs as biomarkers for cancer diagnosis: the Good, the Bad and the Beauty. NPJ Precis Oncol 2022; 6:40. [PMID: 35729321 PMCID: PMC9213432 DOI: 10.1038/s41698-022-00283-7] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 05/13/2022] [Indexed: 11/24/2022] Open
Abstract
Cancer ranks as one of the deadliest diseases worldwide. The high mortality rate associated with cancer is partially due to the lack of reliable early detection methods and/or inaccurate diagnostic tools such as certain protein biomarkers. Cell-free nucleic acids (cfNA) such as circulating long noncoding RNAs (lncRNAs) have been proposed as a new class of potential biomarkers for cancer diagnosis. The reported correlation between the presence of tumors and abnormal levels of lncRNAs in the blood of cancer patients has notably triggered a worldwide interest among clinicians and oncologists who have been actively investigating their potentials as reliable cancer biomarkers. In this report, we review the progress achieved ("the Good") and challenges encountered ("the Bad") in the development of circulating lncRNAs as potential biomarkers for early cancer diagnosis. We report and discuss the diagnostic performance of more than 50 different circulating lncRNAs and emphasize their numerous potential clinical applications ("the Beauty") including therapeutic targets and agents, on top of diagnostic and prognostic capabilities. This review also summarizes the best methods of investigation and provides useful guidelines for clinicians and scientists who desire conducting their own clinical studies on circulating lncRNAs in cancer patients via RT-qPCR or Next Generation Sequencing (NGS).
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Affiliation(s)
- Cedric Badowski
- University of Hawaii Cancer Center, Epidemiology, 701 Ilalo Street, Honolulu, HI, 96813, USA.
| | - Bing He
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48105, USA
| | - Lana X Garmire
- University of Hawaii Cancer Center, Epidemiology, 701 Ilalo Street, Honolulu, HI, 96813, USA.
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48105, USA.
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21
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Yang C, Chen K. Long Non-Coding RNA in Esophageal Cancer: A Review of Research Progress. Pathol Oncol Res 2022; 28:1610140. [PMID: 35241975 PMCID: PMC8885534 DOI: 10.3389/pore.2022.1610140] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 01/26/2022] [Indexed: 12/24/2022]
Abstract
In recent years, there has been significant progress in the diagnosis and treatment of esophageal cancer. However, owing to the lack of early diagnosis strategies and treatment targets, the prognosis of patients with esophageal cancer remains unsatisfactory. There is an urgent need to identify novel biomarkers and treatment targets for esophageal cancer. With the development of genomics, long-chain non-coding RNAs (LncRNAs), which were once considered transcriptional “noise,” are being identified and characterized rapidly in large numbers. Recent research shows that LncRNAs are closely related to a series of steps in tumor development and play an important regulatory role in DNA replication, transcription, and post-transcriptional regulation. The abnormal expression of LncRNAs leads to tumor cell proliferation, migration, invasion, and treatment resistance. This review focuses on the latest progress in research on the abnormal expression and functional mechanisms of LncRNAs in esophageal cancer. Further, it discusses the potential applications of these findings towards achieving an early diagnosis, improving treatment efficacy, and evaluating the prognosis of esophageal cancer.
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Affiliation(s)
- Chenbo Yang
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Pathology, Zhengzhou University, Zhengzhou, China
| | - Kuisheng Chen
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Henan Key Laboratory of Tumor Pathology, Zhengzhou University, Zhengzhou, China
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22
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ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma. NPJ Precis Oncol 2022; 6:12. [PMID: 35233069 PMCID: PMC8888636 DOI: 10.1038/s41698-022-00255-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 02/03/2022] [Indexed: 11/20/2022] Open
Abstract
Long non-coding RNAs (LncRNAs) play important roles in the development of human esophageal squamous cell carcinoma (ESCC). Our previous studies have shown that knockdown of LncRNA ESCCAL-1 expression inhibits the growth of ESCC cells, but the mechanisms remain largely unknown. In this study, we show that over-expression of ESCCAL-1 promotes ESCC cell proliferation and cell-cycle progression by blocking ubiquitin-mediated degradation of an oncoprotein galectin-1 (Gal-1). Multiple LncRNA expression datasets as well as our own data together reveal that ESCCAL-1 is evidently up-regulated in ESCC tissues and exhibits promising diagnostic value. Over-expression of ESCCAL-1 augmented ESCC cell proliferation and cell-cycle progression, whereas down-regulation of ESCCAL-1 resulted in the opposite effects. Mechanistically, LncRNA ESCCAL-1 directly binds to Gal-1 and positively regulates its protein level without affecting its mRNA level. Up-regulation of Gal-1 facilitated ESCC cell proliferation and cell-cycle progress. Knockdown of Gal-1 mitigated the effects of ESCCAL-1-mediated high cellular proliferation, NF-κB signaling activation and tumorigenicity of ESCC cells. Thus, our findings provide novel insight into the mechanism by which ESCCAL-1 facilitates ESCC tumorigenesis and cell-cycle progression by interacting with and stabilizing Gal-1 protein, suggesting a potential therapeutic target for ESCC.
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23
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Jiang C, Li X, Sun B, Zhang N, Li J, Yue S, Hu X. Extracellular vesicles promotes liver metastasis of lung cancer by ALAHM increasing hepatocellular secretion of HGF. iScience 2022; 25:103984. [PMID: 35281743 PMCID: PMC8914534 DOI: 10.1016/j.isci.2022.103984] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/09/2022] [Accepted: 02/21/2022] [Indexed: 11/18/2022] Open
Affiliation(s)
- Chunyang Jiang
- Department of Thoracic Surgery, Tianjin Union Medical Center, Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin, China
- Corresponding author
| | - Xu Li
- Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Bingsheng Sun
- Department of Thoracic Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, Tianjin, China
| | - Na Zhang
- Department of Respiratory Medicine, Tianjin Union Medical Center, Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin, China
| | - Jing Li
- Department of Respiratory Medicine, Tianjin Union Medical Center, Nankai University, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin, China
| | - Shijing Yue
- The State Key Laboratory of Medicinal Chemical Biology, School of Medicine, The State International Science & Technology Cooperation Base of Tumor Immunology and Biological Vaccines, Nankai University, 94 Weijin Road, Nankai District, Tianjin 300071, Tianjin, China
- Corresponding author
| | - Xiaoli Hu
- Department of Respiratory Medicine, The Second People’|'s Hospital of Linhai City, 198 Dubei Road, Linhai 317016, Zhejiang Province, China
- Corresponding author
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24
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Zhao Z, Yang S, Zhou A, Li X, Fang R, Zhang S, Zhao G, Li P. Small Extracellular Vesicles in the Development, Diagnosis, and Possible Therapeutic Application of Esophageal Squamous Cell Carcinoma. Front Oncol 2021; 11:732702. [PMID: 34527593 PMCID: PMC8435888 DOI: 10.3389/fonc.2021.732702] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 08/09/2021] [Indexed: 12/14/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) persists among the most lethal and broad-spreading malignancies in China. The exosome is a kind of extracellular vesicle (EV) from about 30 to 200 nm in diameter, contributing to the transfer of specific functional molecules, such as metabolites, proteins, lipids, and nucleic acids. The paramount role of exosomes in the formation and development of ESCC, which relies on promoting intercellular communication in the tumor microenvironment (TME), is manifested with immense amounts. Tumor-derived exosomes (TDEs) participate in most hallmarks of ESCC, including tumorigenesis, invasion, angiogenesis, immunologic escape, metastasis, radioresistance, and chemoresistance. Published reports have delineated that exosome-encapsulated cargos like miRNAs may have utility in the diagnosis, as prognostic biomarkers, and in the treatment of ESCC. This review summarizes the function of exosomes in the neoplasia, progression, and metastasis of ESCC, which improves our understanding of the etiology and pathogenesis of ESCC, and presents a promising target for early diagnostics in ESCC. However, recent studies of exosomes in the treatment of ESCC are sparse. Thus, we introduce the advances in exosome-based methods and indicate the possible applications for ESCC therapy in the future.
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Affiliation(s)
- Zheng Zhao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shuyue Yang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Anni Zhou
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xiao Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Rui Fang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Guiping Zhao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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25
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Jing Z, Chen K, Gong L. The Significance of Exosomes in Pathogenesis, Diagnosis, and Treatment of Esophageal Cancer. Int J Nanomedicine 2021; 16:6115-6127. [PMID: 34511909 PMCID: PMC8423492 DOI: 10.2147/ijn.s321555] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 08/16/2021] [Indexed: 12/21/2022] Open
Abstract
Esophageal cancer is one of the most common malignancy in China with high mortality. Understanding pathogenesis and identifying early diagnosis biomarkers can significantly improve the prognosis of patients with esophageal cancer. Exosomes are small vesicular structures containing a variety of components (including DNA, RNA, and proteins) mediating cell-to-cell material exchange and signal communication. Growing evidences have shown that exosomes and its components are involved in growth, metastasis and angiogenesis in cancer, and could also be used as diagnostic and prognostic markers. In this review, we summarized recent progress to elucidate the significance of exosomes in the esophageal cancer progression, microenvironment remodeling, therapeutic resistance, and immunosuppression. We also discuss the utility of exosomes as diagnostic and prognostic biomarkers and therapeutic tool in esophageal cancer.
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Affiliation(s)
- Zhao Jing
- Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, People's Republic of China
| | - Kai Chen
- Department of Cardiovascular and Thoracic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Ling Gong
- Department of Infectious Disease (Liver Diseases), The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, People's Republic of China
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Ranjan S, Jain S, Bhargava A, Shandilya R, Srivastava RK, Mishra PK. Lateral flow assay-based detection of long non-coding RNAs: A point-of-care platform for cancer diagnosis. J Pharm Biomed Anal 2021; 204:114285. [PMID: 34333453 DOI: 10.1016/j.jpba.2021.114285] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 07/23/2021] [Accepted: 07/23/2021] [Indexed: 12/13/2022]
Abstract
Lateral flow assay (LFA) is a flexible, simple, low-costpoint-of-care platform for rapid detection of disease-specific biomarkers. Importantly, the ability of the assay to capture the circulating bio-molecules has gained significant attention, as it offers a potential minimal invasive system for early disease diagnosis and prognosis. In the present article, we review an innovative concept of LFA-based detection of circulating long non-coding RNAs (lncRNAs), one of the key regulators of fundamental biological processes. In addition, their disease-specific expression pattern and presence in biological fluids at differential levels make them excellent biomarker candidates for cancer detection. Our article also provides an update on the requirements for developing and improving such systems and discusses the key aspects of material selection, operational concepts, principles and conceptual design. We assume that the reviewed points will be helpful to improve the diagnostic applicability of LFA based lncRNA detection in cancer diagnosis.
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Affiliation(s)
- Shashi Ranjan
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Surbhi Jain
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Arpit Bhargava
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Ruchita Shandilya
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | | | - Pradyumna Kumar Mishra
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India.
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Wang S, Jun J, Cong L, Du L, Wang C. miR-328-3p, a Predictor of Stroke, Aggravates the Cerebral Ischemia-Reperfusion Injury. Int J Gen Med 2021; 14:2367-2376. [PMID: 34135620 PMCID: PMC8197582 DOI: 10.2147/ijgm.s307392] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/14/2021] [Indexed: 12/22/2022] Open
Abstract
Background In the present study, we aimed to identify microRNAs (miRNAs) that affected the prognosis of stroke and assess their biological effects. Materials and Methods A high-throughput sequencing (HTS) analysis was performed to screen distinctive miRNAs in serum exosomes of stroke patients, and these miRNAs were subsequently validated using individual quantitative real-time polymerase chain reaction (qRT-PCR) in a cohort consisting of 39 stroke patients and 20 normal controls. Briefly, miR-328-3p agomir or agomir NC was injected into rats before ischemia and reperfusion (I/R) injury. Zea-Longa score, neurological severity score (mNSS), triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, transmission electron microscopy, and hematoxylin and eosin (H&E) staining were used to examine the brain injury. Immunohistochemistry was utilized to determine the expressions of TNF-α and IL-6. Results The expression of serum exosomal miR-328-3p was significantly reduced in patients with an infarct volume ≥10 cm3 (P=0.01). Serum exosomal miR-328-3p was associated with the short-term prognosis (P=0.02), and the level of miR-328-3p was an independent relative factor for short-term prognosis (OR 5.276, P=0.02). The sensitivity of miR-328-3p level higher than 1.24 to predict the severity of the patient’s 1-week prognosis was 70%, and the specificity was 83% (AUC=0.74, P=0.02). The mNSS was higher in the miR-328-3p agomir group compared with the agomir NC group (P=0.03). Neutrophil infiltration was more serious in the miR-328-3p agomir group. Conclusion Our study indicated that miR-328-3p played a critical predictive role in the short-term prognosis of stroke, and up-regulation of miR-328-3p aggravated cerebral I/R injury.
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Affiliation(s)
- Shun Wang
- Department of Clinical Laboratory, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People's Republic of China
| | - Jiang Jun
- Department of Neurosurgery, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People's Republic of China
| | - Liyuan Cong
- Department of Clinical Laboratory, Community Health Service Center, Qingdao, 266000, Shandong, People's Republic of China
| | - Lutao Du
- Department of Clinical Laboratory, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People's Republic of China
| | - Chuanxin Wang
- Department of Clinical Laboratory, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People's Republic of China
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