Long non-coding RNA SNHG20 predicts a poor prognosis for HCC and promotes cell invasion by regulating the epithelial-to-mesenchymal transition

Biomed Pharmacother. 2017 May:89:857-863. doi: 10.1016/j.biopha.2017.01.011. Epub 2017 Mar 6.

Abstract

Background: Recently, Accumulating evidence indicates that long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human tumor biology and development. However, the expression pattern and biological function of lncRNA small nucleolar RNA host gene 20 (SNHG20) in hepatocellular carcinoma (HCC) remains largely unknown.

Methods: The expression of SNHG20 in 96 paired HCC tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR) analysis. Kaplan-Meier survival analysis and log-rank test was used to reveal the association between SNHG20 expression and the overall survival time in HCC patients. CCK8 cell proliferation and transwell invasion assays were performed to analyze the cell proliferation and cell invasion ability. QRT-PCR and western-blotting analysis were performed to demonstrate the mRNA levels and protein expression of ZEB1, ZEB2 and relative epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin).

Results: We showed that the expression level of SNHG20 was significantly up-regulated in 96 pairs of HCC tissues and adjacent normal tissues. Higher SNHG20 expression was positively correlated with larger tumor size and advanced TNM stage, and negatively correlated with the over survival (OS) time for HCC patients. In vitro, loss-function assays revealed that knockdown of SNHG20 inhibited cell proliferation and invasion, whereas, gain-of-function promoted cell proliferation and invasion. Furthermore, knockdown of SNHG20 inhibited ZEB1, ZEB2, N-cadherin and Vimentin expression and up-regulated the E-cadherin expression in HCC cells. Mechanistic investigation revealed that SNHG20 could bind to enhancer of zeste homolog 2 (EZH2) and regulated E-cadherin expression.

Conclusion: Our results showed that the SNHG20/EZH2/E-cadhein regulator pathway might contribute to the development of novel therapeutic strategies for HCC patients.

Keywords: E-cadherin; Enhancer of zeste homolog 2; Hepatocellular carcinoma; Small nucleolar RNA host gene 20.

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Prognosis
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • RNA, Long Noncoding
  • RNA, Messenger
  • long non-coding RNA SNHG20, human