Rhophilin rho GTPase binding protein 1-antisense RNA 1 (RHPN1-AS1) promotes ovarian carcinogenesis by sponging microRNA-485-5p and releasing DNA topoisomerase II alpha (TOP2A)

Bioengineered. 2021 Dec;12(2):12003-12022. doi: 10.1080/21655979.2021.2002494.

Abstract

Ovarian cancer (OC) is the most common and lethal gynecological cancer worldwide. Long non-coding RNAs (lncRNAs) and sponging microRNAs (miRNAs) serve as key regulators in the biological processes of OC. We sought to evaluate the effect of the RHPN1-AS1-miR-485-5p-DNA topoisomerase II alpha (TOP2A) axis in regulating OC progression. RHPN1-AS1, miR-485-5p, and TOP2A levels in OC tissues and cells were determined by RT-qPCR. The interaction of RHPN1-AS1/miR-485-5p/TOP2A was assessed using luciferase, RNA immunoprecipitation, and RNA pull-down assays. RHPN1-AS1 silencing allowed us to explore its biological function by measuring cell viability, proliferation, migration, invasion, and apoptosis in OC cells. In vivo experiments were performed to verify the in vitro findings. We found that the RHPN1-AS1 and TOP2A levels were significantly enhanced, whereas the miR-485-5p levels were reduced in OC tissues and cells. RHPN1-AS1 silencing attenuated cell growth, facilitated apoptosis in OC cells, and inhibited tumor growth in vivo. Notably, RHPN1-AS1 negatively regulating miR-485-5p promoted the TOP2A expression in OC cells. In conclusion, RHPN1-AS1 sponging miR-485-5p accelerated the progression of OC by elevating TOP2A expression, which makes it a promising target for the treatment of OC patients.

Keywords: RHPN1-as1; TOP2A; apoptosis; invasion; miR-485-5p; migration; ovarian cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA Topoisomerases, Type II / metabolism*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • MIRN485 microRNA, human
  • MicroRNAs
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Long Noncoding
  • long noncoding RNA RHPN1-AS1, human
  • DNA Topoisomerases, Type II
  • TOP2A protein, human

Grants and funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Natural Science Foundation of Hunan Province of China (No. 2019JJ50694) and by the Hunan Provincial Education Commission Foundation (No. 20C0198).