HNRNPA1-mediated 3' UTR length changes of HN1 contributes to cancer- and senescence-associated phenotypes

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 (or ) showed shortening in cancers and lengthening in senescence, correlated well with its high expression in cancer cells and low expression in senescent cells, respectively. transcripts with longer 3' UTR were less stable and produced less protein. Down-regulation of induced senescence-associated phenotypes in both normal and cancer cells. Patients with higher expression had lower survival rates in various carcinomas. Interestingly, down-regulating the splicing factor HNRNPA1 induced 3' UTR lengthening of and senescence-associated phenotypes, which could be partially reversed by overexpressing . Together, we revealed for the first time that HNRNPA1-mediated APA of contributed to cancer- and senescence-related phenotypes. Given senescence is a cancer prevention mechanism, our discovery indicates the HNRNPA1- axis as a potential target for cancer treatment.