Prediction of potential prognostic biomarkers in metastatic prostate cancer based on a circular RNA-mediated competing endogenous RNA regulatory network

PLoS One. 2021 Dec 3;16(12):e0260983. doi: 10.1371/journal.pone.0260983. eCollection 2021.


Recently, studies on competing endogenous RNA (ceRNA) networks have become prevalent, and circular RNAs (circRNAs) have crucial implications for the development and progression of carcinoma. However, studies relevant to metastatic prostate cancer (mPCa) are scant. This study aims to discover potential ceRNAs that may be related to the prognosis of mPCa. RNA-Seq data were obtained from the MiOncoCirc database and Gene Expression Omnibus (GEO). Differential expression patterns of RNAs were examined using R packages. Circular RNA Interactome, miRTarBase, miRDB and TargetScan were applied to predict the corresponding relation between circRNAs, miRNAs and mRNAs. The Gene Ontology (GO) annotations were performed to present related GO terms, and Gene Set Enrichment Analysis (GSEA) tools were applied for pathway annotations. Moreover, survival analysis was conducted for the hub genes. We found 820 circRNAs, 81 miRNAs and 179 mRNAs that were distinguishingly expressed between primary prostate cancer (PCa) and mPCa samples. A ceRNA network including 45 circRNAs, 24 miRNAs and 56 mRNAs was constructed. In addition, the protein-protein interaction (PPI) network was built, and 10 hub genes were selected by using the CytoHubba application. Among the 10 hub genes, survival analysis showed that ITGA1, LMOD1, MYH11, MYLK, SORBS1 and TGFBR3 were significantly connected with disease-free survival (DFS). The circRNA-mediated ceRNA network provides potential prognostic biomarkers for metastatic prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Computational Biology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Molecular Sequence Annotation
  • Neoplasm Metastasis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Interaction Maps*
  • RNA, Circular / genetics*
  • RNA, Messenger / genetics*


  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger

Grant support

This work was supported by Guangdong Provincial Natural Science Foundation of China (2014A030313088, 2017A030313478), Guangdong Provincial Science and Technology Foundation of China (2016A020215073). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.