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

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.