miR-106b-5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3
miR-106b-5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3
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DOI：
10.1002/cam4.2511
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发表时间：
2019-09-10
期刊：
影响因子：
4
通讯作者：
Han, Wei
中科院分区：
文献类型：
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作者：
Gu, Hao;Gu, Shensen;Han, Wei
背景与目的microRNA（miR）-106b-5p在肝细胞癌（HCC）中的作用尚不清楚。本研究旨在探讨miR-106 b-5 p在HCC中表达的临床意义及其机制。方法采用实时荧光定量逆转录聚合酶链反应（real-time reverse transcription PCR，RT-PCR）检测108例HCC临床标本中miR-106 b-5 p的表达水平。分别采用卡方检验、Kaplan-Meier和考克斯比例回归分析评估miR-106 b-5 p表达与各种临床病理特征和患者预后的关系。通过荧光素酶报告基因、CCK-8和Transwell Matrigel侵袭实验研究miR-106 b-5 p的靶基因及其在肝癌细胞中的功能。结果肝癌组织中miR-106 b-5 p的表达明显高于癌旁肝组织（P < .001）。miR-106 b-5 p上调与晚期TNM分期（P = .02）、短期无复发（P = .005）和总体（P = .001）生存率显著相关。重要的是，miR-106 b-5 p表达是预后不良的独立预测因子（P <0.05）。RUNX 3是miR-106 b-5 p在肝癌细胞中的直接靶基因。在功能上，miR-106 b-5 p上调促进HCC细胞的存活力和侵袭，而加强RUNX 3表达逆转miR-106 b-5 p过表达的致癌作用。结论miR-106 b-5 p可作为预测肝癌复发和生存的有效指标。miR-106 b-5 p可能通过调控其靶基因RUNX 3而在HCC中发挥致癌作用。
Background and Objectives The roles of microRNA(miR)-106b-5p in hepatocellular carcinoma (HCC) remain unclear. We aimed here to investigate the clinical significance of miR-106b-5p expression in HCC and its underlying mechanisms. Methods Expression levels of miR-106b-5p in 108 HCC clinical samples by quantitative real-time reverse transcription PCR. Associations of miR-106b-5p expression with various clinicopathological features and patients' prognosis were evaluated by Chi-square test, Kaplan-Meier, and Cox proportional regression analyses, respectively. The target gene of miR-106b-5p and their functions in HCC cells were investigated by luciferase reporter, CCK-8, and Transwell Matrigel invasion assays. Results miR-106b-5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR-106b-5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence-free (P = .005), and overall (P = .001) survivals. Importantly, miR-106b-5p expression was an independent predictor of poor prognosis (P < .05). RUNX3 was identified as a direct target gene of miR-106b-5p in HCC cells. Functionally, miR-106b-5p upregulation promoted the viability and invasion of HCC cells, while enforced RUNX3 expression reversed the oncogenic effects of miR-106b-5p overexpression. Conclusions miR-106b-5p may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. miR-106b-5p may exert an oncogenic role in HCC via regulating its target gene RUNX3.