Overexpression of Exportin-5 Overrides the Inhibitory Effect of miRNAs Regulation Control and Stabilize Proteins via Posttranslation Modifications in Prostate Cancer

• DOI: 10.1016/j.neo.2017.07.008
• Publication Date: 2017-09-04T23:30:42Z
• Authors: Naseruddin Höti; Shuang Yang; Paul Aiyetan; Binod Kumar; Yingwei Hu; David Clark; Arife Unal Eroglu; Punit Shah; Tamara Johnson; Wasim H. Chowdery; Hui Zhang; Ronald Rodriguez
• Keywords: Male; Proteomics; 0301 basic medicine; Original article; Proteome; Protein Stability; Gene Expression Profiling; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Gene Expression; Prostatic Neoplasms; Karyopherins; 3. Good health; MicroRNAs; 03 medical and health sciences; Receptors, Androgen; Cell Line, Tumor; Gene Knockdown Techniques; Animals; Cluster Analysis; Humans; RNA Interference; Protein Processing, Post-Translational; RC254-282; Cell Proliferation

Although XPO5 has been characterized to have tumor-suppressor features in the miRNA biogenesis pathway, impact of altered expression cancers is unexplored. Here we report a novel "oncogenic" role advanced prostate cancer. Using cancer models, found that excess levels override inhibitory effect canoncial miRNA-mRNA regulation, resulting global increase proteins expression. Importantly, decreased could promote an proteasome degradation, whereas overexpression leads protein posttranslational modification via hyperglycosylation, cellular stability. We evaluated therapeutic advantage targeting and knocking down cells suppressed proliferation tumor development without significantly impacting normal fibroblast survival. To our knowledge, this first describing oncogenic overriding miRNAs regulation control. Furthermore, believe these findings will provide explanation as why, some express higher abundance mature miRNAs, fail suppress their potential targets.