Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC

Mol Carcinog. 2018 Jul;57(7):926-935. doi: 10.1002/mc.22813. Epub 2018 Apr 6.

Abstract

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings.

Keywords: HULC; hepatocarcinogenesis; long non-coding RNA; low dose irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Mice
  • Mice, Nude
  • RNA, Long Noncoding / genetics*
  • Radiation Dosage
  • Up-Regulation / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • HULC long non-coding RNA, human
  • RNA, Long Noncoding