The role of human antigen R (HuR) in modulating proliferation, senescence and radiosensitivity of skin cells

Exp Ther Med. 2022 Jul 12;24(3):566. doi: 10.3892/etm.2022.11503. eCollection 2022 Sep.

Abstract

The skin is the largest outermost organ of the human body. It is vulnerable to various damages, such as ionizing radiation. Exploration of proliferation, senescence and radiosensitivity of skin cells contributes to the development of medical and cosmetic countermeasures against skin aging and toward injury protection. Human antigen R (HuR) is one of the most widely studied RNA-binding proteins and serves an important role in stabilization of mRNA and regulation of the expression of the target genes. To investigate the role of HuR in modulating proliferation, senescence and radiosensitivity of skin cells, the present study performed an in vitro study using lentivirus-mediated overexpression or silencing of HuR in human keratinocyte HaCaT cells and human skin fibroblast WS1 cells. The results indicated that overexpression of HuR promoted proliferation, whereas downregulation of HuR inhibited proliferation of HaCaT and WS1 cells. Overexpression of HuR reduced apoptosis and senescence in skin cells. RNA-Seq of skin cells with HuR overexpression or knockdown identified 77 mRNAs positively or negatively correlated with HuR expression levels. In addition, silencing of HuR induced a significant increase in radiogenic reactive oxygen species after irradiation. Overexpression of HuR increased radiotolerance of HaCaT and WS1 cells. RNA immunoprecipitation coupled with RNA-Seq identified 14 mRNAs interacting with HuR upon radiation exposure. Overall, the findings of the present study illustrated the key role of HuR in modulating proliferation, senescence and radiosensitivity of skin cells providing a new therapeutic strategy for cosmetic treatments and to combat skin injury.

Keywords: human antigen R; proliferation; radiosensitivity; senescence; skin.

Grant support

Funding: The present study supported by the National Natural Science Foundation of China (grant nos. 32071238, 82073477 and 31770909), Natural Science Foundation of Sichuan Province (grant no. 2020YJ0194), Natural Science Project of Chengdu Medical College (grant nos. CYZ19-31 and CYZZD20-01) and Young Talent Program of China National Nuclear Corporation.