Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway

Cell Death Dis. 2018 Aug 30;9(9):888. doi: 10.1038/s41419-018-0882-5.

Abstract

Accumulating evidence have suggested that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers. The present study aimed to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in hepatocellular carcinoma (HCC) progression using human tissues and cell lines. The quantitative real-time PCR results showed that SNHG5 was up-regulated in both HCC tissues and hepatoma cell lines and was closely associated with tumor size, hepatitis B virus infection, histologic grade, TNM stage, and portal vein tumor thrombus (PVTT) in HCC patients. Knockdown of SNHG5 induced apoptosis and repressed cell cycle progression, cell growth, and metastasis in hepatoma cell lines, whereas overexpression of SNHG5 had the opposite effects. In vivo functional assay, xenograft tumors grown from SNHG5-knockdown cells had smaller mean volumes than the tumors grown from negative control cells. Further investigations showed that SNHG5 may act as a competing endogenous RNA by competitively binding miR-26a-5p and thereby modulating the derepression of downstream target GSK3β, which were further confirmed by luciferase reporter assay. Functionally, SNHG5 promotes tumor growth and metastasis by activating Wnt/β-catenin pathway and inducing epithelial to mesenchymal transition (EMT). Taken together, SNHG5 promotes HCC progression by competitively binding miR-26a-5p and regulating GSK3β and Wnt/β-catenin signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Hep G2 Cells
  • Hepatitis B / genetics
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Transplantation, Heterologous
  • Wnt Signaling Pathway / genetics

Substances

  • MIRN26A microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • long non-coding RNA SNHG5, human
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta