DAB2IP-Coordinated miRNA Biogenesis
Annual rept. 1 Sep 2014-31 Aug 2015
TEXAS UNIV HEALTH SCIENCE CENTER AT DALLAS
Pagination or Media Count:
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.
- Medicine and Medical Research