MicroRNA-1205 Regulation of FRYL in Prostate Cancer

Frontiers in Cell and Developmental Biology

Tamara Gillot¹  Konstantinos Krampis¹  Thahmina Ali¹  Fayola Levine¹  Michelle Naidoo²  Chun Pan³  Akintunde T. Orunmuyi⁴  E. Oluwabunmi Olapade-Olaopa⁵  Andrea Sboner⁶  Princesca Dorsaint⁶  Olorunseun O. Ogunwobi⁷ 

[1] Department of Biological Sciences, Hunter College of the City University of New York, New York, NY, United States;Department of Biology and Biochemistry, The Graduate Center of the City University of New York, New York, NY, United States;Department of Mathematics and Statistics, Hunter College of the City University of New York, New York, NY, United States;Department of Radiation Oncology, College of Medicine, University of Ibadan, Ibadan, Nigeria;Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria;Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, United States;Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, United States;

关键词: prostate cancer;    FRYL;    microRNA-1205;    neuroendocrine prostate cancer;    neuroendocrine differentiation;   

DOI  :  10.3389/fcell.2021.647485

来源: DOAJ

【 摘 要 】

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 in vivo. 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 in vitro 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.

【 授权许可】

Unknown