CircRNA Cdr1as functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression

Aging (Albany NY). 2019 Oct 1;11(19):8183-8203. doi: 10.18632/aging.102312. Epub 2019 Oct 1.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Recent years, circular RNA (circRNA) have been shown to exert vital functions in the pathological progressions of many diseases. A growing number of evidences have identified the representative function of exosomal circRNAs in the physiological state of donor cells, which further induces cellular responses after captured by recipient cells. However, the contributions of circRNAs to HCC remain largely unknown. In vitro and in vivo regulatory roles of circRNA Cdr1as in proliferative and migratory abilities of HCC were evaluated by CCK8, EdU, Transwell and tumourigenicity assays, respectively. Results showed circRNA Cdr1as was highly expressed in HCC cell lines and tissues. Overexpression of circRNA Cdr1as greatly accelerated HCC cells to proliferate and migrate. Mechanistically, we found that Cdr1as could promote the expression of AFP, a well-known biomarker for HCC, by sponging miR-1270. Further studies showed exosomes extracted from HCC cells overexpressing circRNA Cdr1as accelerated the proliferative and migratory abilities of surrounding normal cells. In all, circRNA Cdr1as serves as a ceRNA to promote the progression of HCC. Meanwhile, it is directly transferred from HCC cells to surrounding normal cells via exosomes to further mediate the biological functions of surrounding cells.

Keywords: AFP; circRNA Cdr1as; competing endogenous RNAs; exosomes; hepatocellular carcinoma.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Liver / cytology
  • Liver Neoplasms / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation

Substances

  • MIRN1270 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Long Noncoding
  • long non-coding RNA CDR1AS, human