MicroRNA-340 inhibits the proliferation and invasion of hepatocellular carcinoma cells by targeting JAK1

Biochem Biophys Res Commun. 2017 Jan 29;483(1):578-584. doi: 10.1016/j.bbrc.2016.12.102. Epub 2016 Dec 18.

Abstract

Increasing evidence indicates that dysregulation of microRNAs (miRNAs) contributes to tumorigenesis. MicroRNA-340 (miR-340) is downregulated in several types of cancer. However, the functional mechanism of miR-340 in hepatocellular carcinoma (HCC) remains unclear. Here, we showed that miR-340 was significantly downregulated in HCC tissues and cell lines. Gain-of-function experiments demonstrated that miR-340 overexpression inhibited HCC cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo. Janus kinase 1 (JAK1) was identified as a direct target of miR-340 in HCC cells. Ectopic expression of JAK1 reversed the inhibitory effects of miR-340. Further investigations showed that miR-340 dramatically inhibited the expression of signal transducer and activator of transcription (STAT)3 downstream molecules including Bcl-2, cyclin D1, and matrix metalloprotease (MMP)-2. The present findings indicated that miR-340 suppressed HCC cell proliferation and invasion by regulating the JAK1/STAT3 pathway, suggesting its potential as a novel therapeutic target for HCC.

Keywords: Hepatocellular carcinoma; Invasion; JAK1/STAT3 pathway; Proliferation; miR-340.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Janus Kinase 1 / metabolism*
  • Liver Neoplasms / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction

Substances

  • MIRN340 microRNA, human
  • MIRN340 microRNA, mouse
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1