An Association of Unique microRNA Turnover Machinery with Prostate Cancer Progression
Abstract
Prostate cancer (PCa) is still incurable when cancer cells undergo epithelial-to-mesenchymal transition (EMT) and acquire cancer stem cell (CSC) phenotypes to become metastatic therapy- and castration-resistant PCa (t-CRPC). In this study, we demonstrate that IFN can induce EMT in PCa cells via the JAK-STAT1 signaling pathway, leading to the transcription of interferon-induced tetratricopeptide repeat 5 (IFIT5). We also unveil a new function of IFIT5 complex in degrading precursor microRNAs (pre-miRNA) that include pre-miR-363 from the miR-106a-363 cluster as well as pre-miR-101 and pre-miR-128. Mechanistically, STAT1-mediated induction of IFIT5 appears to facilitate the acquisition of stemness properties by accelerating specific microRNAs (such as miR-128 and miR-101) turnover, which is resulted in BMI1 and SOX2 elevation. Overall, this study provides a new understanding of the role of IFN-STAT1-IFIT5-mediated microRNA turnover in the acquisition of stemness properties in PCa and also highlights STAT1 as a potent therapeutic target in preventing the outgrowth of t-CRPC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2022
- Accession Number
- AD1153689
Entities
People
- Jer-Tsong Hsieh
Organizations
- University of Texas Southwestern Medical Center