肝细胞癌中miR-942-5p的表达及其与患者恶性特征及不良预后的关系

目的:探讨微小RNA-942-5p(miR-942-5p)在肝细胞癌(HCC)组织中的表达及其功能。方法:用实时定量PCR检测西安交通大学第一附属医院样本库保存的73例HCC组织和对应癌旁组织中miR-942-5p的表达。分析miR-942-5p表达与HCC患者临床病理资料的关系,同时分析TCGA数据库中miR-942-5p表达与HCC患者总生存率的关系。Transwell小室检测干扰miR-942-5p表达后HCC细胞迁移和侵袭能力的变化,StarBase V3.0网站和荧光素酶报告基因质粒预测分析miR-942-5p的下游靶点,并用Western blot验证。结果:miR-942-5p表达量在HCC组织中明显高于对应癌旁组织(2.390 vs. 1.764,P<0.05)。miR-942-5p表达量与HCC患者肿瘤数目、血管浸润和临床分期明显有关(均P<0.05)。miR-942-5p高表达HCC患者总生存率明显低于miR-942-5p低表达HCC患者(19.535%vs. 53.873%,P<0.05)。沉默miR-942-5p表达后,肝癌HCCLM3和MHCC97H细胞迁移和侵袭能力明显减弱(均P<0.05)。预测与分析结果显示,扣针蛋白5(FBLN5)是miR-942-5p的直接下游靶点(P<0.05),沉默miR-942-5p表达导致HCCLM3和MHCC97H细胞中FBLN5表达增加。结论:miR-942-5p在HCC组织中表达异常升高并与恶性临床特征和不良预后密切相关,机制可能与miR-942-5p抑制FBLN5表达促进HCC细胞迁移和侵袭有关。

Expression of microRNA-942-5p in hepatocellular carcinoma and its relations with malignant feature and unfavorable outcomes of the patients

Objective: To investigate the expression of microRNA-942-5p (miR-942-5p) in hepatocellular carcinoma (HCC) tissue and its functions.  Methods: The expressions of miR-942-5p in 73 specimens of HCC tissue and paired tumor-adjacent tissue stored in the specimen bank of the First Affiliated Hospital, Xian Jiaotong University were determined by real-time quantitative PCR, and the relations of miR-942-5p expression with clinicopathologic parameters of HCC patients were analyzed. Meanwhile, the relationship between miR-942-5p expression and overall survival of HCC patients was identified by analyzing TCGA database. The changes in migration and invasion abilities of HCC cells after miR-942-5p expression interference were observed by Transwell assay. The downstream target of miR-942-5p was predicted and identified by using StarBase V3.0 database and Luciferase reporter assay, and then validated by Western blot.   Results: The miR-942-5p expression in HCC tissues was significantly higher than that in tumor-adjacent tissue (2.390 vs. 1.764, P<0.05). The expression level of miR-942-5p was significantly associated with the number of lesions, vascular invasion and tumor stage of HCC patients (all P<0.05). The overall survival rate of HCC patients with high miR-942-5p expression was significantly lower than HCC patients with low miR-942-5p expression (19.535% vs. 53.873%, P<0.05). After silencing the miR-942-5p expression, the migration and invasion abilities of liver cancer HCCLM3 and MHCC97H cells were significantly weakened (both P<0.05). The results of prediction and analysis showed that fiblulin 5 (FBLN5) was a direct downstream target of miR-942-5p (P<0.05). Knockdown of the miR-942-5p expression led to increased expression of FBLN5 in HCCLM3 and MHCC97H cells. Conclusion: The miR-942-5p expression is aberrantly up-regulated in HCC tissue and its overexpression is closely related to the malignant clinical features and poor prognosis. The mechanism may probably be responsible for miR-942-5p inhibiting FBLN5 expression and then promoting migration and invasion of HCC cells.