Competing endogenous network analysis identifies lncRNA Meg3 activates inflammatory damage in UVB induced murine skin lesion by sponging miR-93-5p/epiregulin axis

Aging (Albany NY). 2019 Nov 24;11(22):10664-10683. doi: 10.18632/aging.102483. Epub 2019 Nov 24.

Abstract

In this study, we obtained the RNA expression data of murine skin tissues of control, and UVB irradiated groups. After the re-annotation of lncRNAs, a gene expression similarity analysis was done by WGCNA. The target mRNA prediction of lncRNAs, miRNAs, and ceRNA regulatory networks were constructed by five lncRNAs, 14 miRNAs and 54 mRNAs, respectively. Based on the ceRNA network of UVB-induced skin lesions, it was evident that the dysregulation of Meg3 has critical effects on the UVB-induced inflammatory lesion of murine skin tissues. The overexpression of Meg3 after UVB irradiation was observed in primary murine skin fibroblasts, and the up-regulated Meg3 expression was related to the activation of the inflammatory cytokines. These functional experiments demonstrated that the RNA silencing of Meg3 in murine skin fibroblasts could suppress the expression of the cytokines (in vitro) and UVB-induced skin lesions (in vivo). Moreover, the Meg3 functioned as a competing endogenous RNA (ceRNA) that acted as a sponge for miR-93-5p and thereby modulated the expression of Epiregulin (Ereg). Our results proved that Meg3 was involved in UVB-induced skin inflammation and that the ceRNA networks, which includes miR-93-5p and Ereg, could prove to be a potential therapeutic target for UVB-induced skin damage.

Keywords: ceRNA; inflammatory damage; lncRNA Meg3; skin; ultraviolet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epiregulin / metabolism*
  • Epiregulin / radiation effects
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Gene Expression Regulation / radiation effects
  • Gene Regulatory Networks
  • Inflammation / etiology
  • Inflammation / metabolism*
  • Mice
  • MicroRNAs / metabolism*
  • MicroRNAs / radiation effects
  • RNA, Long Noncoding / metabolism*
  • RNA, Long Noncoding / radiation effects
  • Signal Transduction / physiology
  • Signal Transduction / radiation effects*
  • Skin / metabolism
  • Skin / radiation effects*
  • Ultraviolet Rays / adverse effects*

Substances

  • Epiregulin
  • Ereg protein, mouse
  • MEG3 non-coding RNA, mouse
  • MicroRNAs
  • Mirn93 microRNA, mouse
  • RNA, Long Noncoding