RBM10 regulates human TERT gene splicing and inhibits pancreatic cancer progression.

ABSTRACT: Dysregulation of alternative splicing of hTERT gene to generate full-length Htert (hTERT-FL) that reactivate telomerase has been recognized as a major pathological alteration in pancreatic cancer (PrCa). Mechanism about the factors that regulate hTERT-FL splicing is lacking. Through bioinformatics approach, we focus on a candidate splicing factor RBM10, which leads to a switch in hTERT transcripts to generate a function-less isoform hTERT-s in PrCa, suppressed both telomerase activity and subsequent telomere shortening. RBM10 expression is negatively associated with PrCa progression. Gain or loss of RBM10 also significantly changed PrCa cell proliferation in vitro and in xenografts. RNA-IP and RNA pull-down assays reveal that RBM10 promotes the exclusion of exons7 and 8 which results in the production of TERT-s transcripts. This study may increase knowledge about potentially targetable cancer associated splicing factors and provide novel insights into therapeutic approach in PrCa.

SUBMITTER: Xiao W 

PROVIDER: S-EPMC7840715 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature