Department of Hepatobiliary Surgery, The People's Hospital of Kaizhou District, Chongqing, 405400, PR China.
Department of Hepatobiliary Surgery, The People's Hospital of Kaizhou District, Chongqing, 405400, PR China.
Biomed Pharmacother. 2017 Dec;96:1246-1252. doi: 10.1016/j.biopha.2017.11.090. Epub 2017 Dec 6.
Currently, hepatocellular carcinoma (HCC) patients still have poor survival outcomes mainly due to the powerful mobility of HCC cells. Increasing evidences hint that abnormally expressed miRNAs are capable to modulate HCC cells invasion and migration. MiR-1202 has been proposed as a ponderable molecular tumor marker in a variety of tumors. Here, results from real-time PCR indicated the decreased expression of miR-1202 in HCC. Clinically, statistical analysis showed that miR-1202 under-expression was closely associated with metastasis-related clinicopathologic characteristics. In addition, 5-year overall survival (OS) and disease-free survival (DFS) rates of HCC patients with high miR-1202 expression were much better than that in low miR-1202 group. Functionally, gain- and loss-of -function studies were performed to investigate the roles of miR-1202. Intriguingly, Would healing assay and Transwell assays indicated that elevated miR-1202 weakened HCC cells migration and invasion abilities, while miR-1202 knockdown presented the contrary effects. Furthermore, cyclin dependent kinase 14 (CDK14) was identified as a downstream target of miR-1202 by bioinformatics analysis, Dual luciferase reporter assay, detection of CDK14 expression and Pearson correlation analysis. More importantly, rescue experiments demonstrated that CDK14 mediated miR-1202 to exert its anti-tumor effects, which further confirmed the above finding. Taken together, miR-1202 may act as a new biomarker and potential therapeutic target for HCC.
目前,肝细胞癌 (HCC) 患者的生存率仍然很差,主要是由于 HCC 细胞具有强大的迁移能力。越来越多的证据表明,异常表达的 miRNAs 能够调节 HCC 细胞的侵袭和迁移。miR-1202 已被提出作为多种肿瘤中重要的分子肿瘤标志物。在这里,实时 PCR 的结果表明 HCC 中 miR-1202 的表达降低。临床分析表明,miR-1202 的低表达与转移相关的临床病理特征密切相关。此外,miR-1202 高表达的 HCC 患者的 5 年总生存率 (OS) 和无病生存率 (DFS) 明显好于 miR-1202 低表达组。功能研究表明,进行了 gain- 和 loss-of -function 研究以研究 miR-1202 的作用。有趣的是,划痕愈合实验和 Transwell 实验表明,上调 miR-1202 减弱了 HCC 细胞的迁移和侵袭能力,而 miR-1202 敲低则呈现相反的效果。此外,通过生物信息学分析、双荧光素酶报告基因实验、CDK14 表达检测和 Pearson 相关分析,鉴定出细胞周期蛋白依赖性激酶 14 (CDK14) 是 miR-1202 的下游靶标。更重要的是,挽救实验表明 CDK14 介导 miR-1202 发挥其抗肿瘤作用,进一步证实了上述发现。综上所述,miR-1202 可能作为 HCC 的一个新的生物标志物和潜在的治疗靶点。