miR-216a-5p通过JAK2靶向抑制肝癌细胞的增殖和侵袭

miR-216a-5p suppresses the proliferation and invasion of hepatocellular carcinoma cells through targeting JAK2

目的明确miR-216a-5p在调控肝细胞癌(HCC)中的生物学作用及其可能机制。方法通过实时荧光定量聚合酶链反应(qRT-PCR)方法检测92例HCC患者的肿瘤组织及对应癌旁组织中miR-216a-5p的表达情况。并采用CCK8和Transwell试验检测miR-216a-5p对HCC细胞增殖和侵袭能力的影响。采用荧光素酶、蛋白质印迹和qRT-PCR检测肝细胞癌中miR-216a-5p的表达与JAK2表达的相关性。结果发现miR-216a-5p在HCC中的表达显著降低,并与多种临床病理特征(肿瘤多样性、组织学分化、巴塞罗那分期)相关。低表达miR-216a-5p的HCC患者预后不良。双荧光素报告系统分析证实JAK2是miR-216a-5p的直接下游靶基因。并且过表达JAK2抵消了miR-216a-5p对HCC细胞增殖、迁移和侵袭的抑制能力。结论 miR-216a-5p可能是一种新的潜在的肝癌治疗靶点。

Objective Accumulating evidences have indicated that microRNA (miRNA) dysregulation contributes to hepatocellular carcinoma (HCC) progression. In this study, we investigated the potential function of miR-216a-5p in HCC. Methods Expression of miR-216a-5p in 92 cases of HCC tissues and adjacent normal tissues was determined by using quantitative real-time PCR (qRT-PCR) analyses. In vitro, cell proliferation and invasion capacity were evaluated by CCK8 assay and Transwell invasion assay, respectively. Luciferase reporter assay, Western blot and qRT-PCR were used to detect the association between miR-216a-5p expression and Janus kinase 2 (JAK2) in HCC. Results In this study, we showed that the expression level of miR-216a-5p was significantly decreased in HCC, and was associated with several clinicopathological characteristics, including tumor multiplicity, histological differentiation, and Barcelona clinic liver cancer stage. Low expression level of miR-216a-5p was associated with poor survival outcomes in HCC patients. Upregulation of miR-216a-5p suppressed cell proliferation, migration, and invasion of HCC. Dual luciferase assay demonstrated that JAK2 was a direct downstream target of miR-216a-5p. JAK2 reintroduction restored the inhibited proliferation, migration, and invasion of miR-216a-5p-overexpressed HCC cells. miR-216a-5p functioned as a tumor suppressor to modulate the JAK2/STAT3 signaling pathway. Conclusion The present findings indicate that miR-216a-5p could be used as a prognostic predictor and therapeutic candidate for HCC.