Downregulation of SBF2-AS1 functions as a tumor suppressor in clear cell renal cell carcinoma by inhibiting miR-338-3p-targeted ETS1

Cancer Gene Ther. 2021 Aug;28(7-8):813-827. doi: 10.1038/s41417-020-0197-4. Epub 2020 Jul 28.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of kidney cancer in adults, accompanied by an increasing incidence rate worldwide. We found that SBF2-AS1 was a differentially expressed long-noncoding RNA (lncRNA) in ccRCC through the microarray-based expression analyses. The aim of the present study was to explore the role of SBF2-AS1 in ccRCC development by assessing its effects on cellular processes and further investigate the underlying mechanism. SBF2-AS1 was found to be highly expressed in ccRCC tissues and cells. Ectopic expression and knockdown of SBF2-AS1 and miR-338-3p were performed in ccRCC 768-O cells to explore their effects on cell proliferation, migration, invasion, apoptosis and autophagy by EdU assay, scratch test, Transwell assay, calcein-AM/PI, and GFP-LC3 immunofluorescence assays, respectively. The interactions among SBF2-AS1, miR-338-3p and ETS1 were analyzed using dual-luciferase reporter, RIP and RNA pull-down assays. SBF2-AS1 specifically bound to miR-338-3p and inhibited its expression. Moreover, ETS1 was targeted by miR-338-3p. The knockdown of SBF2-AS1 or ETS1 or overexpression of miR-338-3p resulted in reduced cell proliferation, migration and invasion but elevated cell apoptosis and autophagy. In vivo experiments verified the tumor-suppressive role of silencing SBF2-AS1 in tumor growth of nude mice xenografted with ccRCC cells. Thus, silencing SBF2-AS1 exerted suppressive effects on ccRCC by elevating miR-338-3p and suppressing ETS1.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Middle Aged
  • Proto-Oncogene Protein c-ets-1 / metabolism*

Substances

  • Ets1 protein, mouse
  • MicroRNAs
  • Mirn338 microRNA, mouse
  • Proto-Oncogene Protein c-ets-1