LncRNA SNHG3 promotes clear cell renal cell carcinoma proliferation and migration by upregulating TOP2A

Exp Cell Res. 2019 Nov 1;384(1):111595. doi: 10.1016/j.yexcr.2019.111595. Epub 2019 Sep 7.

Abstract

LncRNA plays a vital role in many diseases, and abnormal expression of LncRNA has been reported in many types of tumors. In this study, we analyzed the available public TCGA and GEO databases, and found that the expression of SNHG3 was increased in clear cell renal cell carcinoma (ccRCC), which was positively correlated with many clinicopathological parameters, and the higher expression of SNHG3 predicted worse clinical prognosis. Functional experiments indicated that knockdown of SNHG3 could significantly inhibit the proliferation and metastasis of ccRCC in vitro and in vivo. Subsequently, through luciferase reporter assays, qPCR and rescue experiments, it was found that SNHG3 could bind to miR-139-5p, thereby up-regulating the expression of its target gene TOP2A, and play a role in promoting tumor progression in ccRCC. The correlation analysis showed that there was a significant positive correlation between the expression of SNHG3 and TOP2A, and both of them were significantly negative correlated with the expression of miR-139-5p. Our work suggested that the SNHG3/miR-139-5p/TOP2A axis plays an important role in the proliferation and metastasis of ccRCC, and was expected to be a new biomarker for diagnosis, prognosis and a target for treatment of ccRCC.

Keywords: Clear cell renal cell carcinoma; SNHG3; TOP2A; miR-139-5p.

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA Topoisomerases, Type II / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • Neoplasm Proteins / genetics*
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Prognosis
  • RNA, Long Noncoding
  • Transcriptional Activation / genetics
  • Up-Regulation / genetics*

Substances

  • MicroRNAs
  • Neoplasm Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Long Noncoding
  • SNHG32 lncRNA, human
  • DNA Topoisomerases, Type II
  • TOP2A protein, human