A Competing Endogenous RNA Network and an 8-lncRNA Prognostic Signature Identify MYO16-AS1 as an Oncogenic lncRNA in Bladder Cancer

DNA Cell Biol. 2021 Jan;40(1):26-35. doi: 10.1089/dna.2020.6014. Epub 2020 Dec 2.

Abstract

Recently, growing evidence has shed light on the competitive endogenous RNAs (ceRNAs) activity of long noncoding RNAs (lncRNAs) in carcinogenesis and tumor progression. To better elucidate the regulatory mechanisms of lncRNA in muscle-invasive bladder cancer (MIBC), we identified aberrantly expressed mRNAs, lncRNAs, and miRNAs in tumor tissues by using RNA sequence profiles from The Cancer Genome Atlas. The MIBC-specific ceRNA network, including 58 lncRNAs, 22 miRNAs, and 52 mRNAs, was constructed and visualized in Cytoscape. Further, using the univariate and multivariate Cox regression model, we screened 8 lncRNAs (AC078778.1, LINC00525, AC008676.1, AP000553.1, SACS-AS1, AC009065.1, AC127496.3, and MYO16-AS1) to construct an lncRNA signature for predicting the overall survival of MIBC patients. Kaplan-Meier analysis and a receiver operating characteristic curve were applied to evaluate the performance of the signature. Real-time quantitative PCR analysis was carried out to test expression levels of the 8 lncRNAs in MIBC patient tissues. Transwell assays demonstrated that overexpressing MYO16-AS1 can enhance UMUC2 migration and invasion. Our study offers a novel lncRNA-correlated ceRNA model to better understand the molecular mechanisms involved in MIBC. In addition, we developed an independent 8-lncRNAs biomarker for prognostic prediction and identified MYO16-AS1 as an oncogenic lncRNA in bladder cancer.

Keywords: MYO16-AS1; The Cancer Genome Atlas; competitive endogenous RNAs; long noncoding RNA; muscle-invasive bladder cancer; prognostic signature.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Female
  • Humans
  • Male
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding