DAB2IP-Coordinated miRNA Biogenesis
Abstract
Prostate cancer (PCa) is the most common male malignancy and the second leading cause of cancer mortality in US. To date, the most difficult task for PCa management is to distinguish between indolent and aggressive castration-resistance PCa (CRPC), which emerges when prostatic epithelial cells undergoing a phenotypic change of epithelial to mesenchymal transition (EMT). The acquisition of EMT in PCa cells increases their invasive potentials leading to metastases. In this study, we unveil the unique function of miRNA-363 (miR-363), often down regulated in high-grade PCa, as a potent anti-EMT microRNAs (miRNA). Noticeably, although miR-363 belongs to the miR-106a-363 cluster, the rest of miRNAs in this cluster closely resemble the oncogenic miR-17-92 cluster. Also, no miR-363 homolog is present in the miR-17-92 cluster. Our work provides a mechanistic insight of miR-363 regulation within the miR-106a-363 cluster by interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) characterized as a viral RNA binding protein. IFIT5 appears to coordinate with XRN1and specifically mediate miR-363 turnover but not other miRNAs in this cluster. IFIT5 is highly elevated in high-grade PCa. Thus, this study delineates a novel machinery of the turnover of a tumor suppressive miRNA within a cluster containing mostly oncogenic miRNAs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- ADA624651
Entities
People
- U-ging Lo
Organizations
- University of Texas at Austin