MicroRNA‑378b regulates α‑1‑type 1 collagen expression via sirtuin 6 interference

Mol Med Rep. 2017 Dec;16(6):8520-8524. doi: 10.3892/mmr.2017.7657. Epub 2017 Sep 28.

Abstract

Ultraviolet (UV) light mediates skin aging and induces destruction of the dermis by modulating the expression levels of extracellular matrix‑associated genes, including collagen and matrix metalloproteinases. Sirtuin 6 (SIRT6), a member of the sirtuin family of proteins, regulates collagen metabolism and is an established anti‑aging protein. However, the exact underlying mechanism by which SIRT6 expression is regulated in dermal fibroblasts during the aging process is unclear. The present study demonstrated that expression of microRNA‑378b (miR‑378b) is induced in UVB‑exposed human dermal fibroblasts (HDFs), and this was inversely associated with the mRNA expression levels of α‑1‑type 1 collagen (COL1A1). In addition, knockdown of miR‑378b enhanced the mRNA expression levels of COL1A1 in HDFs. A target analysis for miR‑378b was performed, and the results revealed that SIRT6, a regulator of COL1A1, contains a target sequence for miR‑378b in its 3'untranslated region. Notably, the present study demonstrated that an miR‑378b mimic and inhibitor may directly regulate SIRT6 expression in HDFs. In conclusion, the present study suggested that miR‑378b represses the mRNA expression levels of COL1A1 via interference with SIRT6 in HDFs, and may contribute to the underlying molecular mechanism by which UVB inhibits collagen I in dermal fibroblasts.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Collagen Type I / genetics*
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Dermis / cytology
  • Down-Regulation / radiation effects
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • Gene Expression Regulation / radiation effects*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Binding / radiation effects
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Ultraviolet Rays

Substances

  • 3' Untranslated Regions
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • MIRN378 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • SIRT6 protein, human
  • Sirtuins