Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma

Aging (Albany NY). 2019 Nov 23;11(22):10422-10453. doi: 10.18632/aging.102468. Epub 2019 Nov 23.

Abstract

The abnormal expression of noncoding RNAs has attracted increasing interest in the field of hepatocellular carcinoma progression. However, the underlying molecular mechanisms mediated by noncoding RNAs in these processes are unclear. Here, we obtained the expression profiles of long noncoding RNAs, microRNAs, and mRNAs from the Gene Expression Omnibus database and identified hepatocarcinogenesis-specific differentially expressed transcripts. Next, we identified significant Gene Ontology and pathway terms that the differentially expressed transcripts involved in. Using functional analysis and target prediction, we constructed a hepatocellular carcinoma-associated deregulated competitive endogenous RNA network to reveal the potential mechanisms underlying tumor progression. By analyzing The Cancer Genome Atlas dataset, six key long noncoding RNAs showed significant association with overall survival as well as strong correlation with some microRNAs and mRNAs in the competitive endogenous RNA network. We further validated the above results and determined their diagnostic and prognostic value in clinical samples. Importantly, by large-scale analyses, we identified a cluster of long noncoding RNAs, GBAP1, MCM3AP-AS1, SLC16A1-AS1, C3P1, DIO3OS, and HNF4A-AS1 as candidate biomarkers for the diagnosis and prognosis of hepatocellular carcinoma, which will improve our understanding of competitive endogenous RNA-mediated regulatory mechanisms underlying hepatocellular carcinoma development and will provide novel therapeutic targets in the future.

Keywords: CeRNA; hepatocellular carcinoma; lncRNA; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Regulatory Networks / genetics*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • RNA, Long Noncoding / genetics*
  • Transcriptome

Substances

  • RNA, Long Noncoding