Up-regulation of SNHG6 activates SERPINH1 expression by competitive binding to miR-139-5p to promote hepatocellular carcinoma progression

Cell Cycle. 2019 Aug;18(16):1849-1867. doi: 10.1080/15384101.2019.1629772. Epub 2019 Jul 1.

Abstract

We aimed to assess the roles of small nucleolar RNA host gene 6 (SNHG6) in hepatocellular carcinoma (HCC) progression, and establish the lncRNA-miRNA-mRNA regulation mechanism for HCC therapy. SNHG6 is one of the host genes in small nucleolar RNAs (snoRNAs), which make a difference in the development of human cancers. SERPINH1 is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors with miRNA predicted by TargetScan and DIANA Tools. SNHG6, serpin family H member 1 (SERPINH1) and miR-139-5p expression levels in HCC tissues and cells were determined by quantitative real-time PCR (qRT-PCR). Migration and invasion of HCC cells were measured by transwell assay. Cell cycle analysis was determined by using flow cytometry. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony formation assay were performed for cell viability analysis. The expression of SERPINH1 was detected by qRT-PCR and western blot. Dual-luciferase reporter gene assay was conducted to identify the targeted relationship between miR-139-5p and SNHG6, as well as SERPINH1 and miR-139-5p. The positive regulation between SNHG6 and SERPINH1 was demonstrated in this study. In contrast, miR-139-5p was significantly down-regulated in HCC cells, the inhibition of miR-139-5p promotes the proliferation of HCC cells, and accelerated the cell cycle of HCC cells. Our study demonstrated the co-expression of SNHG6 and SERPINH1 in HCC cells for the first time, which revealed that SNHG6 could serve as a novel oncogene for the HCC therapy by its regulation.

Keywords: Hepatocellular carcinoma; SERPINH1; SNHG6; miR-139-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / genetics*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HSP47 Heat-Shock Proteins / genetics
  • HSP47 Heat-Shock Proteins / metabolism*
  • Hep G2 Cells
  • Hepatocytes / metabolism
  • Heterografts
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transfection
  • Up-Regulation / genetics*

Substances

  • HSP47 Heat-Shock Proteins
  • MIRN139 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SERPINH1 protein, human
  • long non-coding RNA SNHG6, human

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (Grant No.: 81302161) and the Health and Family Planning Commission of Sichuan Province (Grant No.: 150215).