Characterization of unique PMEPA1 gene splice variants (isoforms d and e ) from RNA Seq profiling provides novel insights into prognostic evaluation of prostate cancer.

Prostate cancer is a disease with heterogeneity of multiple gene transcriptomes and biological signaling pathways involved in tumor development. The prostate transmembrane protein, androgen induced 1 (), a multifunctional protein played critical roles in prostate tumorigenesis. The pleiotropic nature of in modulating androgen and TGF-β signaling as well as splice variants mechanisms for functional regulations of cancer-associated genes prompted us to investigate the biological roles of isoforms in prostate cancer. In addition to 4 reported isoforms (, , and ), one novel isoform was identified with RNA Seq analysis of hormone responsive VCaP, LNCaP cells and human prostate cancer samples from The Cancer Genome Atlas (TCGA) dataset. We analyzed the structures, expressions, biological functions and clinical relevance of isoform and less characterized isoforms and in the context of prostate cancer and AR/TGF-β signaling. The expression of was induced by androgen and AR. In contrast, was responsive to TGF-β and inhibited TGF-β signaling. Both and promoted the growth of androgen independent prostate cancer cells. Although was responsive to TGF-β, it was found to have no impacts on cell growth and androgen/TGF-β signaling. The TCGA data analysis from 499 patients showed higher expression ratios of versus or strongly associated with enhanced Gleason score. Taken together, our findings first time defined the prostate tumorigenesis mediated by and isoforms, providing novel insights into the new strategies for prognostic evaluation and therapeutics of prostate tumor.