hnRNP A1 antagonizes cellular senescence and senescence‐associated secretory phenotype via regulation of SIRT1 mRNA stability

• DOI: 10.1111/acel.12511
• Publication Date: 2016-09-10T04:07:06Z
• Authors: Hui Wang; Limin Han; Ganye Zhao; Hong Shen; Pengfeng Wang; Zhaomeng Sun; Chenzhong Xu; Yuanyuan Su; Guodong Li; Tanjun Tong; Jun Chen
• Keywords: Senescence; Sirtuin 1

Senescent cells display a senescence-associated secretory phenotype (SASP) which contributes to tumor suppression, aging, and cancer. However, the underlying mechanisms for SASP regulation are not fully elucidated. SIRT1, nicotinamide adenosine dinucleotide-dependent deacetylase, plays multiple roles in metabolism, inflammatory response, longevity, etc. its posttranscriptional cellular senescence still elusive. Here, we identify RNA-binding protein hnRNP A1 as regulator of well cell regulator. directly interacts with 3' untranslated region SIRT1 mRNA, promotes stability, increases expression. delays replicative prevents from Ras OIS via upregulation expression deacetylate NF-κB, thus blunting transcriptional activity subsequent IL-6/IL-8 induction. overexpression transformation tumorigenesis SIRT1-dependent manner. Together, our findings unveil novel by uncover critical role A1-SIRT1-NF-κB pathway regulating