Role of AUF1 in modulating the proliferation, migration and senescence of skin cells

Abstract

AU-rich element RNA-binding factor 1 (AUF1) is a classical RNA-binding protein. AUF1 influences the process of development, apoptosis and tumorigenesis by interacting with adenylate-uridylate rich element-bearing mRNAs. Human skin is the largest organ of the body and acts as a protective barrier against pathogens and injuries. The aim of the present study was to explore the function and potential molecular pathways of AUF1 in human skin cells. AUF1 was overexpressed in human keratinocyte HaCaT cells and human skin fibroblast WS1 cells using adenoviruses and silenced using lentiviruses. AUF1 overexpression facilitated cell proliferation, whereas AUF1 knockdown induced the opposite effect. AUF1 reduced apoptosis but did not affect cell cycle progression. Forced AUF1 expression promoted the migration of human skin cells, as demonstrated by a scratch wound healing assay. Cell senescence was alleviated in AUF1-overexpressing skin cells, while AUF1 knockdown increased cell senescence. WS1 cells with AUF1 overexpression and silencing were used for RNA-sequencing and Kyoto Encyclopedia of Genes and Genomes-based pathway analysis to identify AUF1-affected mRNAs. A total of 18 mRNAs (eight mRNAs with positive associations and 10 mRNAs with negative associations) revealed consistent associations with both AUF1 overexpression and silencing. Enriched pathways associated with AUF1 expression included ‘MAPK’, ‘cell adhesion molecules’, ‘proteasome’, ‘cellular senescence’ and ‘TGF-β signaling’, indicating a complex regulatory network. Overall, the results of the present study revealed that AUF1 is involved in the proliferation, migration and senescence of skin cells in vitro and may be a potential target for cosmetic and disease treatment of skin.

RNA binding proteins as mediators of pathological cardiac remodeling

“…In addition to these tantalizing bits of data suggesting a prominent role for AUF1 in cardiomyocyte pathophysiology, there are also reports of AUF1 regulation of proliferation, migration, and cell senescence in skin and breast cancer associated fibroblasts that have gone unrealized in the cardiac field ( Hendrayani et al, 2014 ; Wallis et al, 2015 ; Hendrayani et al, 2016 ; Yu et al, 2022 ).…”

AUF1 modulates apoptosis via regulating transcription and alternative splicing of immune response genes in auditory hair cells

“…Therefore, these data hinted at the signi cance of AUF1 in the process of oncogenesis (20). A study on human skin cells recently suggested that the overexpression of AUF1 promoted migration and proliferation of human skin cells, accelerated the healing of wounded skin, and AUF1 overexpression inhibited cell apoptosis, the knockdown of which promoted cell senescence (21).…”