Long non-coding RNA ROR promotes radioresistance in hepatocelluar carcinoma cells by acting as a ceRNA for microRNA-145 to regulate RAD18 expression

Arch Biochem Biophys. 2018 May 1;645:117-125. doi: 10.1016/j.abb.2018.03.018. Epub 2018 Mar 17.

Abstract

Radiotherapy plays a limited role in the treatment of hepatocellular carcinoma (HCC) due to the development of resistance. Therefore, further investigation of underlying mechanisms involved in HCC radioresistance is warranted. Increasing evidence shows that long non-coding RNAs (linc-RNAs) are involved in the pathology of various tumors, including HCC. Previously, we have shown that long noncoding RNA regulator of reprogramming (linc-ROR) promotes HCC metastasis via induction of epithelial-mesenchymal transition (EMT). However, the roles of linc-ROR in HCC radioresistance and its possible mechanisms are unclear. Here, we established two radioresistant HCC cell lines (HepG2-R and SMMC-7721-R) and found that linc-ROR was significantly upregulated in radioresistant HCC cells. Knockdown of linc-ROR reduces in vitro and in vivo radiosensitivity of parental HCC cells by reducing DNA repair capacity, while ectopic expression of linc-ROR enhances radiosensitivity of radioresistant HCC cells. Further mechanistic investigations revealed that lincRNA-ROR exerted its biological effects by acting as a competing endogenous RNA (ceRNA) for miR-145 to regulate RAD18 expression, thereby promoting DNA repair. Collectively, our findings demonstrate that linc-ROR promotes HCC radioresistance and targeting it will be a promising strategy for enhancing the efficacy of radiotherapies in HCC.

Keywords: Hepatocellular carcinoma; Linc-ROR; RAD18; Radioresistance; miR-145.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Carcinoma, Hepatocellular / pathology*
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / pathology*
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Radiation Tolerance / genetics*
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • DNA-Binding Proteins
  • Linc-RNA-RoR, human
  • MIRN145 microRNA, human
  • MicroRNAs
  • RAD18 protein, human
  • RNA, Long Noncoding
  • Ubiquitin-Protein Ligases