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Wei QY, Jin F, Wang ZY, Li BJ, Cao WB, Sun ZY, Mo SJ. MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:1497-1523. [PMID: 38617454 PMCID: PMC11008420 DOI: 10.3748/wjg.v30.i11.1497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/12/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.
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Affiliation(s)
- Qi-Ying Wei
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Feng Jin
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhong-Yu Wang
- Department of Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Bing-Jie Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Wen-Bo Cao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhi-Yan Sun
- Division of Special Service, Department of Basic Oncology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sai-Jun Mo
- Department of Basic Science of Oncology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Qing M, Peng J, Shang Q, Xu H, Chen Q. Effect of Marital Status on Upper Digestive Tract Tumor Survival: Married Male Patients Exhibited a Better Prognosis. Front Surg 2022; 9:880893. [PMID: 35478729 PMCID: PMC9035669 DOI: 10.3389/fsurg.2022.880893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 03/10/2022] [Indexed: 12/24/2022] Open
Abstract
PurposeMarital status has been associated with the outcomes in several types of cancer, but less is known about upper digestive tract tumors (UDTTs). The study aims to explore the effect of marital status on the survival outcomes of UDTT.MethodsWe collected patient cases of UDTT using the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2016. The univariate analyses of overall survival (OS) and cancer-specific survival (CSS) were performed using the Kaplan–Meier method. The multivariate survival analyses were performed using Cox proportional hazard model.ResultsA total of 282,189 patients were included, with 56.42, 16.30, 13.33, and 13.95% of patients married, never married, divorced or separated, and widowed, respectively. The significant differences were observed among married, never-married, divorced or separated, and widowed patients with regard to the year of diagnosis, sex, age, race, pathological type, anatomical site, the number of primary tumor, grade, rate of surgery performed, radiotherapy, chemotherapy (p < 0.001). The proportions of patients with 3-year and 5-year OS were 54.22 and 48.02% in the married group, 46.96 and 41.12% in the never-married group, 44.24 and 38.06% in the divorced or separated group, 34.59 and 27.57% in the widowed group, respectively (p < 0.001); the proportions of patients with 3-year and 5-year CSS were 70.76 and 68.13% in the married group, 62.44 and 59,93% in the never-married group, 63.13 and 60.53% in the divorced or separated group, 62.11 and 58.89% in the widowed group, respectively (p < 0.001); all these data indicated married patients exhibited favorable OS and CSS than never-married, divorced or separated, and widowed patients. Men in the married group showed better OS (HR, 1.16; 95%CI: 1.11–1.22) and CSS (HR, 0.96; 95%CI: 0.92–1.23) than those in the never-married group.ConclusionThis study reveals that marital status is an independent prognostic factor for OS and CSS of patients with UDTT. Married male patients with UDTT trend to have a better prognosis.
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MicroRNA-202 inhibits cell migration and invasion through targeting FGF2 and inactivating Wnt/β-catenin signaling in endometrial carcinoma. Biosci Rep 2020; 39:BSR20190680. [PMID: 31533968 PMCID: PMC6822492 DOI: 10.1042/bsr20190680] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 08/29/2019] [Accepted: 09/13/2019] [Indexed: 12/13/2022] Open
Abstract
Recently, many mircroRNAs (miRNAs) involved in the development and progression of cancer have been reported to regulate cell growth and metastasis, including microRNA-202 (miR-202). The purpose of the present study was to elucidate the effect of miR-202 on endometrial carcinoma (EC) cell migration and invasion. First, qRT-PCR showed that miR-202 was down-regulated in EC tissues, which was associated with poor prognosis in EC patients. Functionally, transwell assay indicated that miR-202 inhibited cell migration and invasion in EC cells. In addition, miR-202 also blocked epithelial-mesenchymal transition (EMT) through suppressing N-cadherin and Vimentin expressions and promoting E-cadherin expression. Moreover, the dual-luciferase reporter assay showed that fibroblast growth factor 2 (FGF2) is a direct target gene for miR-202 in EC cells. Furthermore, up-regulation of FGF2 attenuated the inhibitory effect of miR-202 on cell migration and invasion in EC. Besides that, miR-202 inactivated the Wnt/β-catenin signaling by suppressing β-catenin expression in EC. In conclusion, miR-202 inhibited cell migration and invasion by targeting FGF2 and inactivating the Wnt/β-catenin signaling in EC.
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Kim J, Park S, Hwang D, Kim SI, Lee H. Diagnostic Value of Circulating miR-202 in Early-Stage Breast Cancer in South Korea. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:340. [PMID: 32659906 PMCID: PMC7404566 DOI: 10.3390/medicina56070340] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 07/04/2020] [Accepted: 07/07/2020] [Indexed: 02/06/2023]
Abstract
Background and objectives: Breast cancer is the most common cancer among women worldwide. Early stage diagnosis is important for predicting increases in treatment success rates and decreases in patient mortality. Recently, circulating biomarkers such as circulating tumor cells, circulating tumor DNA, exosomes, and circulating microRNAs have been examined as blood-based markers for the diagnosis of breast cancer. Although miR-202 has been studied for its function or expression in breast cancer, its potential diagnostic value in a clinical setting remains elusive and miR-202 has not been investigated in South Korea. In this study, we aimed to evaluate the diagnostic utility of miR-202 in plasma samples of breast cancer patients in South Korea. Materials and Methods: We investigated miR-202 expression in the plasma of 30 breast cancer patients during diagnosis along with 30 healthy controls in South Korea by quantitative reverse transcription PCR. Results: The results showed that circulating miR-202 levels were significantly elevated in the breast cancer patients compared with those in healthy controls (p < 0.001). The sensitivity and specificity of circulating miR-202 were 90.0% and 93.0%, respectively. Additionally, circulating miR-202 showed high positivity at early stage. The positive rate of miR-202 was as follows: 100% (10/10) for stage I, 90% (9/10) for stage II, and 80% (8/10) for stage III. miR-202 was also a predictor of a 9.6-fold high risk for breast cancer (p < 0.001). Conclusions: Additional alternative molecular biomarkers for diagnosis and management of pre-cancer patients are needed. Circulating miR-202 might be potential diagnostic tool for detecting early stage breast cancer.
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Affiliation(s)
- Jungho Kim
- Department of Biomedical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea;
| | - Sunyoung Park
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Gangwon, Korea; (S.P.); (D.H.)
- School of Mechanical Engineering, Yonsei University, Seoul 03772, Korea
| | - Dasom Hwang
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Gangwon, Korea; (S.P.); (D.H.)
| | - Seung Il Kim
- Department of Surgery, College of Medicine, Yonsei University, Seoul 03772, Korea
| | - Hyeyoung Lee
- Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Gangwon, Korea; (S.P.); (D.H.)
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Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix. Cells 2020; 9:cells9020455. [PMID: 32079295 PMCID: PMC7072790 DOI: 10.3390/cells9020455] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/05/2020] [Accepted: 02/13/2020] [Indexed: 02/06/2023] Open
Abstract
In the last years, the extracellular matrix (ECM) has been reported as playing a relevant role in esophageal cancer (EC) development, with this compartment being related to several aspects of EC genesis and progression. This sounds very interesting due to the complexity of this highly incident and lethal tumor, which takes the sixth position in mortality among all tumor types worldwide. The well-established increase in ECM stiffness, which is able to trigger mechanotransduction signaling, is capable of regulating several malignant behaviors by converting alteration in ECM mechanics into cytoplasmatic biochemical signals. In this sense, it has been shown that some molecules play a key role in these events, particularly the different collagen isoforms, as well as enzymes related to its turnover, such as lysyl oxidase (LOX) and matrix metalloproteinases (MMPs). In fact, MMPs are not only involved in ECM stiffness, but also in other events related to ECM homeostasis, which includes ECM remodeling. Therefore, the crucial role of distinct MMPs isoform has already been reported, especially MMP-2, -3, -7, and -9, along EC development, thus strongly associating these proteins with the control of important cellular events during tumor progression, particularly in the process of invasion during metastasis establishment. In addition, by distinct mechanisms, a vast diversity of glycoproteins and proteoglycans, such as laminin, fibronectin, tenascin C, galectin, dermatan sulfate, and hyaluronic acid exert remarkable effects in esophageal malignant cells due to the activation of oncogenic signaling pathways mainly involved in cytoskeleton alterations during adhesion and migration processes. Finally, the wide spectrum of interactions potentially mediated by ECM may represent a singular intervention scenario in esophageal carcinogenesis natural history and, due to the scarce knowledge on the cellular and molecular mechanisms involved in EC development, the growing body of evidence on ECM’s role along esophageal carcinogenesis might provide a solid base to improve its management in the future.
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Yang C, Yao C, Tian R, Zhu Z, Zhao L, Li P, Chen H, Huang Y, Zhi E, Gong Y, Xue Y, Wang H, Yuan Q, He Z, Li Z. miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling. MOLECULAR THERAPY-NUCLEIC ACIDS 2018; 14:1-19. [PMID: 30513418 PMCID: PMC6280020 DOI: 10.1016/j.omtn.2018.10.012] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 10/15/2018] [Accepted: 10/19/2018] [Indexed: 01/15/2023]
Abstract
MicroRNAs (miRNAs) play important roles in mammalian spermatogenesis, which is highly dependent on Sertoli cells. However, the functions and mechanisms of miRNAs in regulating human Sertoli cells remain largely unknown. Here, we report that hsa-miR-202-3p mediates the proliferation, apoptosis, and synthesis function of human Sertoli cells. miR-202-3p was upregulated in Sertoli cells of Sertoli cell-only syndrome (SCOS) patients compared with obstructive azoospermia (OA) patients with normal spermatogenesis. Overexpression of miR-202-3p induced Sertoli cell apoptosis and inhibited cell proliferation and synthesis, and the effects were opposite when miR-202-3p was knocked down. Lipoprotein receptor-related protein 6 (LRP6) and Cyclin D1 of the Wnt/β-catenin signaling pathway were identified as direct targets of miR-202-3p in Sertoli cells, which were validated by bioinformatics tools and dual-luciferase reporter assay. Differentially expressed LRP6 and Cyclin D1 between OA and SCOS Sertoli cells were also verified. LRP6 small interfering RNA (siRNA) interference not only mimicked the effects of miR-202-3p overexpression, but also antagonized the effects of miR-202-3p inhibition on Sertoli cells. Collectively, miR-202-3p controls the proliferation, apoptosis, and synthesis function of human Sertoli cells via targeting LRP6 and Cyclin D1 of the Wnt/β-catenin signaling pathway. This study thus provides a novel insight into fate determinations of human Sertoli cells and niche of human testis.
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Affiliation(s)
- Chao Yang
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; Nanjing Medical University, 101 Longmian Dadao, Jiangning District, Nanjing 210029, China
| | - Chencheng Yao
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China
| | - Ruhui Tian
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Zijue Zhu
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Liangyu Zhao
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Peng Li
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Huixing Chen
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Yuhua Huang
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Erlei Zhi
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Yuehua Gong
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Yunjing Xue
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Hong Wang
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
| | - Qingqing Yuan
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai 200135, China
| | - Zuping He
- Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; School of Medicine, Hunan Normal University, 371 Tongzipo Road, Changsha, Hunan 410013, China.
| | - Zheng Li
- Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China.
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Jaeger A, Hadlich F, Kemper N, Lübke-Becker A, Muráni E, Wimmers K, Ponsuksili S. MicroRNA expression profiling of porcine mammary epithelial cells after challenge with Escherichia coli in vitro. BMC Genomics 2017; 18:660. [PMID: 28836962 PMCID: PMC5571640 DOI: 10.1186/s12864-017-4070-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 08/16/2017] [Indexed: 12/14/2022] Open
Abstract
Background Coliform mastitis is a symptom of postpartum dysgalactia syndrome (PDS), a multifactorial infectious disease of sows. Our previous study showed gene expression profile change after bacterial challenge of porcine mammary epithelial cells (PMECs). These mRNA expression changes may be regulated through microRNAs (miRNAs) which play critical roles in biological processes. Therefore, miRNA expression profile was investigated in PMECs. Results PMECs were isolated from three lactating sows and challenged with heat-inactivated potential mastitis-causing pathogen Escherichia coli (E. coli) for 3 h and 24 h, in vitro. At 3 h post-challenge with E. coli, target gene prediction identified a critical role of miRNAs in regulation of host immune responses and homeostasis of PMECs mediated by affecting pathways including cytokine binding (miR-202, miR-3277, miR-4903); IL-10/PPAR signaling (miR-3277, miR-4317, miR-548); and NF-ĸB/TNFR2 signaling (miR-202, miR-2262, miR-885-3p). Target genes of miRNAs in PMECs at 24 h were significantly enriched in pathways associated with interferon signaling (miR-210, miR-23a, miR-1736) and protein ubiquitination (miR-125, miR-128, miR-1280). Conclusions This study provides first large-scale miRNA expression profiles and their predicted target genes in PMECs after contact with a potential mastitis-causing E. coli strain. Both, highly conserved miRNAs known from other species as well as novel miRNAs were identified in PMECs, representing candidate predictive biomarkers for PDS. Time-dependent pathogen clearance suggests an important role of PMECs in inflammatory response of the first cellular barrier of the porcine mammary gland. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-4070-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- A Jaeger
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - F Hadlich
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - N Kemper
- Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Foundation, D-30559, Hannover, Germany
| | - A Lübke-Becker
- Institute of Microbiology and Epizootics, Department of Veterinary Medicine at the Freie Universität Berlin, D-14163, Berlin, Germany
| | - E Muráni
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - K Wimmers
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany
| | - S Ponsuksili
- Institute for Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, D-18196, Dummerstorf, Germany.
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Zhang J, Liu W, Jin Y, Jia P, Jia K, Yi M. MiR-202-5p is a novel germ plasm-specific microRNA in zebrafish. Sci Rep 2017; 7:7055. [PMID: 28765643 PMCID: PMC5539161 DOI: 10.1038/s41598-017-07675-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 06/30/2017] [Indexed: 12/19/2022] Open
Abstract
Gametogenesis is a complicated biological process by which sperm and egg are produced for genetic transmission between generations. In many animals, the germline is segregated from the somatic lineage in early embryonic development through the specification of primordial germ cells (PGCs), the precursors of gametes for reproduction and fertility. In some species, such as fruit fly and zebrafish, PGCs are determined by the maternally provided germ plasm which contains various RNAs and proteins. Here, we identified a germ plasm/PGC-specific microRNA miR-202-5p for the first time in zebrafish. MiR-202-5p was specifically expressed in gonad. In female, it was expressed and accumulated in oocytes during oogenesis. Quantitative reverse transcription PCR and whole mount in situ hybridization results indicated that miR-202-5p exhibited a typical germ plasm /PGC-specific expression pattern throughout embryogenesis, which was consistent with that of the PGC marker vasa, indicating that miR-202-5p was a component of germ plasm and a potential PGC marker in zebrafish. Our present study might be served as a foundation for further investigating the regulative roles of miRNAs in germ plasm formation and PGC development in zebrafish and other teleost.
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Affiliation(s)
- Jing Zhang
- Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-sen University, Guangdong, China
| | - Wei Liu
- Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-sen University, Guangdong, China
| | - Yilin Jin
- Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-sen University, Guangdong, China
| | - Peng Jia
- Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-sen University, Guangdong, China
| | - Kuntong Jia
- Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-sen University, Guangdong, China.
| | - Meisheng Yi
- Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-sen University, Guangdong, China.
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Yang J, Fan B, Zhao Y, Fang J. MicroRNA-202 inhibits cell proliferation, migration and invasion of glioma by directly targeting metadherin. Oncol Rep 2017; 38:1670-1678. [PMID: 28714009 DOI: 10.3892/or.2017.5815] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 06/02/2017] [Indexed: 11/06/2022] Open
Abstract
Glioma is the most common and aggressive type of primary malignant brain tumour. Increasing evidence has revealed that microRNAs play important roles in multiple biological processes related to glioma occurrence, development, diagnosis, treatment and prognosis. MicroRNA-202 (miR-202) has been studied in several types of human cancer, whereas the biological roles of miR-202 in glioma remain unknown. The present study, aimed to investigate the expression, clinical significance and biological roles of miR-202 in glioma, as well as its underlying molecular mechanism. We found that miR-202 was significantly downregulated in glioma tissues and cell lines. Low miR-202 expression was associated with Karnofsky performance status (KPS) score and World Health Organization (WHO) grade of glioma patients. Functional assays revealed that ectopic expression of miR-202 inhibited cell proliferation, migration and invasion of glioma. In addition, metadherin (MTDH) was identified as a direct target gene of miR-202 in glioma through bioinformatic analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Furthermore, MTDH expression was upregulated and negatively correlated with miR-202 expression in clinical glioma tissues. MTDH knockdown had similar roles to miR-202 overexpression in glioma cells. Rescue experiments revealed that upregulation of MTDH reversed the suppression of glioma cell growth and metastasis by miR-202. Moreover, miR-202 impaired the PI3K/Akt and Wnt/β-catenin pathways. These results highlight the tumour-suppressive effect of miR-202 in glioma, thereby suggesting that miR-202 may be a potential therapeutic target for the treatment of patients with this malignancy.
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Affiliation(s)
- Jinsheng Yang
- Department of Neurosurgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
| | - Bo Fan
- Department of Neurosurgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
| | - Yachao Zhao
- Department of Neurosurgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
| | - Junchao Fang
- Department of Neurosurgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
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Zhao Z, Lv B, Zhang L, Zhao N, Lv Y. miR-202 functions as a tumor suppressor in non-small cell lung cancer by targeting STAT3. Mol Med Rep 2017; 16:2281-2289. [PMID: 28656198 DOI: 10.3892/mmr.2017.6841] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 03/31/2017] [Indexed: 11/06/2022] Open
Abstract
MicroRNAs (miRNAs) are a group of non-protein‑coding, short single-stranded RNAs, which are considered as promising molecular markers and therapeutic targets in several cancers. The present study explored the expression patterns and functional roles of miR‑202 in non‑small cell lung cancer (NSCLC). The expression levels of miR‑202 were determined in NSCLC tissues and cell lines using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The functional impact of miR‑202 overexpression on NSCLC cell viability, migration and invasion were evaluated using Cell Counting Kit‑8 reagent and Transwell migration and invasion assays, respectively. The molecular mechanism underlying the tumor suppressive roles of miR‑202 on NSCLC was examined using bioinformatics analysis, luciferase reporter assay, RT‑qPCR and western blot analysis. In addition, signal transducer and activator of transcription (STAT) 3 was overexpressed to investigate the impact on miR‑202‑mediated tumor suppression in NSCLC. The results indicated that miR‑202 was downregulated in NSCLC tissues and cell lines, and was associated with tumor node metastasis stage and lymph node metastasis. Exogenous miR‑202 expression reduced NSCLC cell viability, migration and invasion. Furthermore, STAT3 was identified as a direct target gene of miR‑202 in NSCLC. STAT3 overexpression improved miR‑202‑impaired cell viability, migration and invasion. In conclusion, the present study revealed novel anticancer effects induced by miR‑202 upregulation in NSCLC, and indicated that STAT3 may be a molecular target of miR‑202.
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Affiliation(s)
- Zhonghai Zhao
- Department of Thoracic Surgery, Yidu Central Hospital of Weifang, Qingzhou, Shandong 262500, P.R. China
| | - Bin Lv
- Department of Thoracic Surgery, Yidu Central Hospital of Weifang, Qingzhou, Shandong 262500, P.R. China
| | - Li Zhang
- Department of Thoracic Surgery, Yidu Central Hospital of Weifang, Qingzhou, Shandong 262500, P.R. China
| | - Nana Zhao
- Department of Thoracic Surgery, Yidu Central Hospital of Weifang, Qingzhou, Shandong 262500, P.R. China
| | - Yan Lv
- Department of Thoracic Surgery, Anqiu People's Hospital, Anqiu, Shandong 262100, P.R. China
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