MicroRNA-1205 Regulation of FRYL in Prostate Cancer.

TitleMicroRNA-1205 Regulation of FRYL in Prostate Cancer.
Publication TypeJournal Article
Year of Publication2021
AuthorsNaidoo M, Levine F, Gillot T, Orunmuyi AT, E Olapade-Olaopa O, Ali T, Krampis K, Pan C, Dorsaint P, Sboner A, Ogunwobi OO
JournalFront Cell Dev Biol
Volume9
Pagination647485
Date Published2021
ISSN2296-634X
Abstract

High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (CRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). The 8q24 chromosomal locus is a region of very high PCa susceptibility that carries genetic variants associated with high risk of PCa incidence. This region also carries frequent amplifications of the PVT1 gene, a non-protein coding gene that encodes a cluster of microRNAs including, microRNA-1205 (miR-1205), which are largely understudied. Herein, we demonstrate that miR-1205 is underexpressed in PCa cells and tissues and suppresses CRPC tumors . To characterize the molecular pathway, we identified and validated fry-like (FRYL) as a direct molecular target of miR-1205 and observed its overexpression in PCa cells and tissues. FRYL is predicted to regulate dendritic branching, which led to the investigation of FRYL in neuroendocrine PCa (NEPC). Resistance toward ADT leads to the progression of treatment related NEPC often characterized by PCa neuroendocrine differentiation (NED), however, this mechanism is poorly understood. Underexpression of miR-1205 is observed when NED is induced and inhibition of miR-1205 leads to increased expression of NED markers. However, while FRYL is overexpressed during NED, FRYL knockdown did not reduce NED, therefore revealing that miR-1205 induces NED independently of FRYL.

DOI10.3389/fcell.2021.647485
Alternate JournalFront Cell Dev Biol
PubMed ID34386489
PubMed Central IDPMC8354587
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