Analysis of competing endogenous RNA network identifies a poorly differentiated cancer-specific RNA signature for hepatocellular carcinoma

J Cell Biochem. 2020 Mar;121(3):2303-2317. doi: 10.1002/jcb.29454. Epub 2019 Oct 23.

Abstract

Plenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well-differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA-related overall survival (OS) curves were determined using the Kaplan-Meier method. The lncRNA ARHGEF7-AS2 was markedly correlated with OS in HCC (P = .041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7-AS2 expression were associated with notably shorter survival time (P = .038). In addition, the area under the curve values of the lncRNA signature for 1-, 3-, and 5-year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C-index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7-AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7-AS2 may be used as an independent biomarker to predict the prognosis of HCC.

Keywords: ceRNA network; hepatocellular carcinoma; lncRNA; poorly differentiation; prognostic biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • RNA, Antisense / genetics
  • RNA, Long Noncoding / genetics*
  • Rho Guanine Nucleotide Exchange Factors / antagonists & inhibitors
  • Rho Guanine Nucleotide Exchange Factors / genetics
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • ARHGEF7 protein, human
  • Biomarkers, Tumor
  • MIRN92 microRNA, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • Rho Guanine Nucleotide Exchange Factors