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.

miR29a and miR378b Influence CpG-Stimulated Dendritic Cells and Regulate cGAS/STING Pathway

“…Ma found that miRNA-29 family members control the immune system and host-pathogen interactions and influence cytokine (IFN, TNF, and interleukin) signaling in response to bacterial and viral infections [38]. The miR-378 family was observed to influence cell proliferation, and to suppress tumour growth and angiogenesis through various signaling pathways and cytokine production patterns [39][40][41][42][43][44][45]. Our findings show that miR-29a increases IFN-β production and decreases the expression of TNF-α.…”

miR-378b Regulates Insulin Sensitivity by Targeting Insulin Receptor and p110α in Alcohol-Induced Hepatic Steatosis

“…miR-378b, a member of the miR-378 family, is highly conserved across species, from chimp to humans. A previous study has shown that miR-378b is expressed in normal human dermal fibroblasts, and circulating miR-378b is a sensitive biomarker for photo-aging (Joo et al, 2017). It was also found to protect dermal fibroblasts from UVB-inhibited collagen I by targeting SIRT6 (Kim et al, 2017).…”

Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment

“…In this sense, molecular circuits between miRNAs and EMT-TFs have been elucidated, such as that one involving miR-200 and ZEB1 [20]. Other examples involve miRNA-29, miRNA-378b, and miRNA-26a-5p, which are direct regulators of EMT and fibrosis through collagen expression by several mechanisms, such as by inhibiting sirtuin-6 and the autophagic protein ULK-1 [21][22][23]. Main molecular mechanisms underlying EMT activation.…”