Long noncoding RNA RBMS3-AS3 acts as a microRNA-4534 sponge to inhibit the progression of prostate cancer by upregulating VASH1

Gene Ther. 2020 Apr;27(3-4):143-156. doi: 10.1038/s41434-019-0108-1. Epub 2019 Nov 11.

Abstract

Long noncoding RNAs (lncRNAs) have been demonstrated to participate in the progression of many malignancies, including prostate cancer by serving as sponges of microRNAs (miRNAs). Initial microarray-based analysis screened out the poorly expressed lncRNA RBMS3-AS3 in prostate cancer, followed by the identification of putative binding sites with miR-4534 and its target VASH1. Therefore, the present study set out to investigate the potential role of RBMS3-AS3/miR-4534/VASH1 axis in the development of prostate cancer. The biological functions of RBMS3-AS3, miR-4534, and VASH1 on cell proliferation, migration, invasion, and angiogenesis of prostate cancer were evaluated via gain- and loss-of-function experiments. Furthermore, tumor xenograft in nude mice was performed to examine tumorigenesis in vivo. The obtained results indicated that RBMS3-AS3 was poorly expressed in prostate cancer tissues and cells. Of note, overexpression of RBMS3-AS3 was found to suppress cell proliferation, migration, invasion, and angiogenesis as well as the tumorigenic ability of prostate cancer. VASH1 was verified as a target gene of miR-4534. VASH1 expression was found to be downregulated in prostate cancer tissues and cells. Interestingly, RBMS3-AS3 was observed to competitively bind to miR-4534 to upregulate VASH1 expression, resulting in a suppressive role in prostate cancer development. Also, in vitro findings were reproduced in vivo on tumor xenograft in nude mice. Taken together, the present study provides evidence suggesting that RBMS3-AS3 acts as a miR-4534 sponge to inhibit the development of prostate cancer by upregulating VASH1, highlighting a theoretical target for prostate cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prostatic Neoplasms / therapy*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNAi Therapeutics / methods*
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • VASH1 protein, human