Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
Department of Hepatobiliary Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
Oncol Rep. 2017 Aug;38(2):843-849. doi: 10.3892/or.2017.5772. Epub 2017 Jun 30.
MicroRNAs (miRNAs) play critical roles in hepatocellular carcinoma (HCC). However, the expression and biological function of miR-345 in HCC remain unknown. The present study demonstrated that miR-345 expression was reduced in HCC tissues and cell lines. Decreased miR-345 expression was associated with unfavorable clinical features and poor prognosis. In vitro functional assays showed that miR-345 overexpression inhibited the migration and invasion of MHCC-97H cells while miR-345 knockdown promoted metastatic behavior of Hep3B cells. In vivo experiments showed that miR-345 overexpression inhibited while miR-345 knockdown promoted lung metastasis of HCC cells in nude mice. Mechanically, YAP1 was identified to be the downstream target of miR-345 in HCC cells. YAP1 overexpression reversed the inhibitory effects of miR-345 on MHCC-97H migration and invasion, while YAP1 knockdown reduced the promoting effects of miR-345 knockdown on the metastatic behavior of Hep3B cells.
微小 RNA(miRNAs)在肝细胞癌(HCC)中发挥着关键作用。然而,miR-345 在 HCC 中的表达和生物学功能仍不清楚。本研究表明,miR-345 在 HCC 组织和细胞系中表达降低。miR-345 表达降低与不利的临床特征和预后不良相关。体外功能测定表明,miR-345 过表达抑制 MHCC-97H 细胞的迁移和侵袭,而 miR-345 敲低促进 Hep3B 细胞的转移行为。体内实验表明,miR-345 过表达抑制 HCC 细胞在裸鼠中的肺转移,而 miR-345 敲低促进转移。在机制上,YAP1 被鉴定为 HCC 细胞中 miR-345 的下游靶标。YAP1 过表达逆转了 miR-345 对 MHCC-97H 迁移和侵袭的抑制作用,而 YAP1 敲低减少了 miR-345 敲低对 Hep3B 细胞转移行为的促进作用。