HNRNPAl-mediated 3 ' UTR length changes of HN1 contributes to cancer- and senescence-associated phenotypes

Jia, Qi1; Nie, Hongbo2; Yu, Peng1; Xie, Baiyun1; Wang, Chenji3; Yang, Fu4; Wei, Gang1; Ni, Ting1

2019-07-15

10.18632/aging.102060

Aging-US   影响因子和分区

1945-4589

Cellular senescence has been regarded as a mechanism of tumor suppression. Studying the regulation of gene expression at various levels in cell senescence will shed light on cancer therapy. Alternative polyadenylation (APA) regulates gene expression by altering 3' untranslated regions (3' UTR) and plays important roles in diverse biological processes. However, whether APA of a specific gene functions in both cancer and senescence remains unclear. Here, we discovered that 3' UTR of HN1 (or JPT1) showed shortening in cancers and lengthening in senescence, correlated well with its high expression in cancer cells and low expression in senescent cells, respectively. HN1 transcripts with longer 3' UTR were less stable and produced less protein. Down-regulation of HN1 induced senescence-associated phenotypes in both normal and cancer cells. Patients with higher HN1 expression had lower survival rates in various carcinomas. Interestingly, down-regulating the splicing factor HNRNPA1 induced 3' UTR lengthening of HN1 and senescence-associated phenotypes, which could be partially reversed by overexpressing HN1. Together, we revealed for the first time that HNRNPA1-mediated APA of HN1 contributed to cancer- and senescence-related phenotypes. Given senescence is a cancer prevention mechanism, our discovery indicates the HNRNPA1-HN1 axis as a potential target for cancer treatment.

cancer senescence alternative polyadenylation HN1 HNRNPA1

SCI

英语

其他

National Science Foundation of China[31771336] ; National Science Foundation of China[31521003]

Cell Biology ; Geriatrics & Gerontology

Cell Biology ; Geriatrics & Gerontology

WOS:000475849100011

IMPACT JOURNALS LLC

Web of Science

1.Fudan Univ, State Key Lab Genet Engn, Collaborat Innovat Ctr Genet & Dev, Human Phenome Inst,Sch Life Sci, Shanghai 200438, Peoples R China
2.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China
3.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China
4.Second Mil Med Univ, Dept Med Genet, Shanghai 200433, Peoples R China

Jia, Qi,Nie, Hongbo,Yu, Peng,et al. HNRNPAl-mediated 3 ' UTR length changes of HN1 contributes to cancer- and senescence-associated phenotypes[J]. Aging-US,2019,11(13):4407-4437.

Jia, Qi.,Nie, Hongbo.,Yu, Peng.,Xie, Baiyun.,Wang, Chenji.,...&Ni, Ting.(2019).HNRNPAl-mediated 3 ' UTR length changes of HN1 contributes to cancer- and senescence-associated phenotypes.Aging-US,11(13),4407-4437.

Jia, Qi,et al."HNRNPAl-mediated 3 ' UTR length changes of HN1 contributes to cancer- and senescence-associated phenotypes".Aging-US 11.13(2019):4407-4437.