hnRNP A1 promotes keratinocyte cell survival post UVB radiation through PI3K/Akt/mTOR pathway

Jianguo Feng; Yi Liao; Xichao Xu; Qian Yi; Ling He; Liling Tang

doi:10.1016/j.yexcr.2017.12.002

hnRNP A1 promotes keratinocyte cell survival post UVB radiation through PI3K/Akt/mTOR pathway

Exp Cell Res. 2018 Jan 15;362(2):394-399. doi: 10.1016/j.yexcr.2017.12.002. Epub 2017 Dec 8.

Authors

Jianguo Feng¹, Yi Liao², Xichao Xu³, Qian Yi⁴, Ling He³, Liling Tang⁵

Affiliations

¹ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China; Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
² Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China; Department of Cardiothoracic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China.
³ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
⁴ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China; Department of Physiology, College of preclinical medicine，Southwest Medical University, Luzhou, Sichuan Province, China.
⁵ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China. Electronic address: tangliling@cqu.edu.cn.

PMID: 29229447
DOI: 10.1016/j.yexcr.2017.12.002

Abstract

hnRNP A1 acts as a critical splicing factor in regulating many alternative splicing events in various physiological and pathophysiological progressions. hnRNP A1 is capable of regulating UVB-induced hdm2 gene alternative splicing according to our previous study. However, the biological function and underlying molecular mechanism of hnRNP A1 in cell survival and cell cycle in response to UVB irradiation are still unclear. In this study, silencing hnRNP A1 expression by siRNA transfection led to decreased cell survival after UVB treatment, while promoting hnRNP A1 by lentiviruse vector resulted in increased cell survival. hnRNP A1 remarkably enhanced PI3K/Akt/mTOR signaling pathway by increasing phosphorylation of Akt, mTOR and P70S6 protein. Inhibition of PI3K/Akt signaling by LY294002 suppressed the expression of hnRNP A1. While mTOR signaling inhibitors, rapamycin and AZD8055, did not influence hnRNP A1 expression in HaCaT cells, suggesting that hnRNP A1 may be an upstream mediator of mTOR signaling. Furthermore, hnRNP A1 could alleviate UVB-provoked cell cycle arrest at G0/G1 phase and promoted cell cycle progression at G2/M phase. Our results indicate that hnRNP A1 promotes cell survival and cell cycle progression following UVB radiation.

Keywords: Cell cycle; Cell survival; HnRNP A1; PI3K/Akt/mTOR signaling; UVB irradiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing / drug effects
Alternative Splicing / genetics*
Cell Cycle Checkpoints / drug effects
Cell Proliferation / drug effects*
Cell Survival / drug effects
Gene Expression Regulation, Neoplastic / drug effects
HEK293 Cells
Heterogeneous Nuclear Ribonucleoprotein A1 / genetics*
Humans
Keratinocytes / drug effects*
Keratinocytes / metabolism
Morpholines / pharmacology
Phosphatidylinositol 3-Kinases / genetics
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-mdm2 / genetics
Signal Transduction / drug effects
Sirolimus / pharmacology
TOR Serine-Threonine Kinases / genetics

Substances

Heterogeneous Nuclear Ribonucleoprotein A1
Morpholines
(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2
MTOR protein, human
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Sirolimus