Circular RNA circMBOAT2 promotes prostate cancer progression via a miR-1271-5p/mTOR axis

Aging (Albany NY). 2020 Jul 9;12(13):13255-13280. doi: 10.18632/aging.103432. Epub 2020 Jul 9.

Abstract

Patients with advanced prostate cancer (PCa) have poor prognosis. Circular RNAs (circRNAs) regulate biological processes in a variety of cancers, but the precise roles of circRNAs in PCa are poorly understood. Herein, we identified a novel circRNA, termed circMBOAT2 (has_circ_0007334), which was significantly overexpressed in PCa tissues and cell lines. Overexpression of circMBOAT2 was associated with high Gleason score, advanced pathological T stage, and poor prognosis. Overexpression of circMBOAT2 promoted proliferation, migration, and invasion of PCa cells in vitro, and enhanced tumorigenesis and metastasis in vivo. Mechanistically, circMBOAT2 overexpression upregulated the expression of mTOR by acting as a decoy for miR-1271-5p, resulting in the activation of the PI3K/Akt pathway, ultimately promoting the progression of PCa. Importantly, application of an inhibitor of mTOR significantly antagonized circMBOAT2-mediated PCa tumorigenesis in vivo. circMBOAT2 promotes proliferation and metastasis of PCa through miR-1271-5p/mTOR axis-mediated activation of the PI3K/Akt pathway. In summary, our findings uncover a molecular mechanism in the progression of PCa and indicate that circMBOAT2 may be a useful prognostic biomarker and therapeutic target in PCa.

Keywords: PI3K/Akt; circMBOAT2; mTOR; metastasis; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cohort Studies
  • Computational Biology
  • Disease Progression
  • Disease-Free Survival
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • RNA, Circular / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics*
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MIRN1271 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus