nc886, a non-coding RNA, inhibits UVB-induced MMP-9 and COX-2 expression via the PKR pathway in human keratinocytes

Biochem Biophys Res Commun. 2019 May 14;512(4):647-652. doi: 10.1016/j.bbrc.2019.01.068. Epub 2019 Jan 23.

Abstract

nc886, a long non-coding RNA (ncRNA) of 101 nucleotides in length, is known as a vault RNA or microRNA precursor. Despite the recent discovery that ncRNAs in the nucleus play a crucial role in regulating chromosomal transformation and transcription, only a few studies have focused on the function of ncRNAs in the cytoplasm, such as nc886. Several studies have investigated the function of nc886 as a suppressor of carcinogenesis and inflammation in different cancer cell types; however, its role in the skin has yet to be clearly elucidated. The two RNA binding sites for protein kinase RNA-activated (PKR) are located in the central region of the stable structure of nc886, which competes with other double-stranded RNA species. Successful binding results in decreased PKR activity. Among changes in skin cells induced by ultraviolet B (UVB) radiation, nc886 expression decreases, whereas PKR phosphorylation via mitogen-activated protein kinases (MAPKs) increases. Reduced nc886 expression leads to uncontrolled PKR activity and increases in the expression of inflammatory cytokines, matrix metalloproteinase-9 (MMP-9), type IV collagenase, and cyclooxygenase (COX-2), which ultimately accelerate inflammatory responses and skin aging. The present study investigated the regulatory mechanism associated with PKR activity and nc886-PKR binding in skin cell aging and inflammation. These results suggest a role for nc886 in controlling photoaging and inflammation in skin cells.

Keywords: Inflammatory mediators; Keratinocytes; PKR signaling; Skin aging; UVB; nc886.

MeSH terms

  • Cell Line
  • Cyclooxygenase 2 / genetics*
  • Down-Regulation / radiation effects
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects*
  • Matrix Metalloproteinase 9 / genetics*
  • MicroRNAs / genetics
  • RNA, Long Noncoding / genetics*
  • Skin Aging / radiation effects
  • Ultraviolet Rays* / adverse effects
  • Up-Regulation / radiation effects

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 9