| 陶元平,姚乃心,黄智平.MiR-373-3p靶向YWHAZ抑制肝细胞癌增殖和转移能力的研究[J].中国肿瘤,2019,28(7):549-556. |
| MiR-373-3p靶向YWHAZ抑制肝细胞癌增殖和转移能力的研究 |
| MiR-373-3p Functions as Tumor Suppressor in Hepatocellular Carcinoma by Targeting YWHAZ |
| 投稿时间：2018-09-17 |
| DOI：10.11735/j.issn.1004-0242.2019.07.A013 |
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| 中文关键词: 肝细胞癌 miR-373-3p YWHAZ 细胞增殖 细胞侵袭 |
| 英文关键词:hepatocellular carcinoma miR-373-3p YWHAZ cell proliferation cell invasion |
| 基金项目:上海市卫计委青年基金(20164Y0189)；国家自然科学基金创新团体(81521091)；国家人类资源平台 (2005DKA21300)；上海市卫生和计划生育委员会科研课题青年项目(20154Y0083) |
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| 中文摘要: |
| 摘 要：［目的］ 探讨miR-373-3p在肝细胞癌中的生物学作用和分子机制。［方法］ 用miR-373-3p模拟物或miR-373-3p抑制剂转染肝细胞癌细胞系。通过MTT、克隆形成和Transwell实验鉴定miR-373-3p对肝细胞癌细胞增殖和迁移能力的影响。Western blot和实时荧光定量逆转录聚合酶链反应（real-time quantitative reverse transcription PCR，qRT-PCR）检测相关基因蛋白和mRNA的表达水平。采用双荧光素酶法验证miR-373-3p与YWHAZ的关系。［结果］ QRT-PCR检测显示，miR-373-3p在肝癌组织中的表达明显低于癌旁组织，且miR-373-3p的低表达与肝癌患者的肿瘤大小、血管浸润和不良预后显著相关。体外细胞学实验结果显示，过表达miR-373-3p能够显著抑制肝癌细胞的增殖和侵袭能力，而下调miR-373-3p的表达则作用相反。双荧光素酶报告、qRT-PCR和Western blot实验证实，miR-373-3p能够直接靶向YWHAZ的3′-非翻译区(UTR)且抑制YWHAZ在肝癌细胞中的表达。过表达的YWHAZ能够抵消miR-373-3p对肝细胞癌细胞增殖和转移的抑制作用。［结论］ MiR-373-3p可能是一种新的潜在的肝癌治疗靶点。 |
| 英文摘要: |
| Abstract：［Purpose］To investigate the biological function and molecular mechanism of miR-373-3p in hepatocellular carcinoma. ［Methods］ Hepatocellular carcinoma(HCC) cells were transfected with miR-373-3p mimics or miR-373-3p inhibitor. Proliferation and migration were identified by MTT assay，colony formation and transwell assays. Protein and mRNA expression levels of associated genes were measured by Western blot and real-time quantitative reverse transcription PCR(qRT-PCR). Dual luciferase assay was used to determine the relation of miR-373-3p to YWHAZ gene. ［Results］ The results of qRT-PCR assay demonstrated that expression of miR-373-3p was significantly lower in HCC tissues compared with adjacent liver tissues. The lower miR-373-3p expression significantly associated with tumor size，vascular infiltration and poor prognostic outcome in HCC patients. In vitro，ectopic overexpression of miR-373-3p significantly inhibited cell proliferation and invasion capability，while down-regulated miR-373-3p had reversed effects. Furthermore，luciferase reporter gene assay，qRT-PCR，and Western blot assays demonstrated that miR-373-3p targeted 3′-untranslated region(UTR) of YWHAZ gene and inhibited its expression in HCC cells. Overexpression of YWHAZ partially abolished the tumor suppressing effects induced by upregulating miR-373-3p in HCC cells. ［Conclusion］ MiR-373-3p might represent a novel potentially therapeutic target for HCC. |
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