Identification of the Competing Endogenous RNA Networks in Oxidative Stress Injury of Melanocytes

DNA Cell Biol. 2021 Feb;40(2):192-208. doi: 10.1089/dna.2020.5455. Epub 2021 Jan 20.

Abstract

Competing endogenous RNAs (ceRNAs), including long noncoding RNA (lncRNA), circular RNA (circRNA), pseudogenes, synthetic miRNA inhibitors, etc. are classes of RNAs that can compete and interact with each other within an organism. There are regions in these RNAs that can be bound by messenger-RNA-interfering complementary RNA (microRNA), called microRNA response elements (MREs). These RNAs compete with each other to combine complementary microRNAs and MREs to form ceRNA regulatory mechanisms and participate in the regulation of many biological processes. The oxidative stress injury of melanocytes is one of the crucial mechanisms of vitiligo. However, it is unclear whether the ceRNA regulation mechanism is involved in the oxidative stress injury of melanocytes. The purpose of this study is to explore the changes of messenger RNA (mRNA), lncRNAs, and circRNAs in melanocytes under oxidative stress and to identify the key ceRNA regulatory networks. Compared with the normal cells, the chip detection of ceRNA expression profile showed that the expression of 491 mRNAs, 865 lncRNAs, and 1161 circRNAs were altered more than fivefold during the oxidative stress injury of melanocytes. The oxidative stress-related genes (SOD2, PTGS2, DHFR, HMOX1, FOSL1, and PARP1), cell cycle-related genes (CDK1, CCNB1, CCNA2, OIP5, and MK167), and apoptosis-related gene (BIRC5) were identified in the formation of ceRNA regulation networks with lncRNAs and circRNAs, which shares the common MREs. Further verification found that LNCV6_120941_PI430048170 or hsa_circ_0048910 might regulate the expression of SOD2 by sponging hsa-miR-4755-3p, LNCV6_119109_PI430048170, or hsa_circ_0048909 might regulate the expression of HMOX1 by sponging hsa-miR-6721-5p in the oxidative stress injury of melanocytes. In conclusion, complex changes of the ceRNA regulatory network in the oxidative stress response of melanocytes are evident. Oxidative stress may mediate melanocyte injury through the ceRNA regulation mechanism and induce the pathogenesis of vitiligo.

Keywords: ceRNA; circRNA; lncRNA; melanocyte; oxidative stress injury.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Cycle / radiation effects
  • Gene Ontology
  • Gene Regulatory Networks* / drug effects
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Melanocytes / cytology
  • Melanocytes / drug effects
  • Melanocytes / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics*
  • RNA / genetics*

Substances

  • RNA
  • Hydrogen Peroxide