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MicroRNA-1205 Regulation of FRYL in Prostate Cancer

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 th...

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Autores principales: Naidoo, Michelle, Levine, Fayola, Gillot, Tamara, Orunmuyi, Akintunde T., Olapade-Olaopa, E. Oluwabunmi, Ali, Thahmina, Krampis, Konstantinos, Pan, Chun, Dorsaint, Princesca, Sboner, Andrea, Ogunwobi, Olorunseun O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354587/
https://www.ncbi.nlm.nih.gov/pubmed/34386489
http://dx.doi.org/10.3389/fcell.2021.647485
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author Naidoo, Michelle
Levine, Fayola
Gillot, Tamara
Orunmuyi, Akintunde T.
Olapade-Olaopa, E. Oluwabunmi
Ali, Thahmina
Krampis, Konstantinos
Pan, Chun
Dorsaint, Princesca
Sboner, Andrea
Ogunwobi, Olorunseun O.
author_facet Naidoo, Michelle
Levine, Fayola
Gillot, Tamara
Orunmuyi, Akintunde T.
Olapade-Olaopa, E. Oluwabunmi
Ali, Thahmina
Krampis, Konstantinos
Pan, Chun
Dorsaint, Princesca
Sboner, Andrea
Ogunwobi, Olorunseun O.
author_sort Naidoo, Michelle
collection PubMed
description 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.
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spelling pubmed-83545872021-08-11 MicroRNA-1205 Regulation of FRYL in Prostate Cancer Naidoo, Michelle Levine, Fayola Gillot, Tamara Orunmuyi, Akintunde T. Olapade-Olaopa, E. Oluwabunmi Ali, Thahmina Krampis, Konstantinos Pan, Chun Dorsaint, Princesca Sboner, Andrea Ogunwobi, Olorunseun O. Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-07-27 /pmc/articles/PMC8354587/ /pubmed/34386489 http://dx.doi.org/10.3389/fcell.2021.647485 Text en Copyright © 2021 Naidoo, Levine, Gillot, Orunmuyi, Olapade-Olaopa, Ali, Krampis, Pan, Dorsaint, Sboner and Ogunwobi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Naidoo, Michelle
Levine, Fayola
Gillot, Tamara
Orunmuyi, Akintunde T.
Olapade-Olaopa, E. Oluwabunmi
Ali, Thahmina
Krampis, Konstantinos
Pan, Chun
Dorsaint, Princesca
Sboner, Andrea
Ogunwobi, Olorunseun O.
MicroRNA-1205 Regulation of FRYL in Prostate Cancer
title MicroRNA-1205 Regulation of FRYL in Prostate Cancer
title_full MicroRNA-1205 Regulation of FRYL in Prostate Cancer
title_fullStr MicroRNA-1205 Regulation of FRYL in Prostate Cancer
title_full_unstemmed MicroRNA-1205 Regulation of FRYL in Prostate Cancer
title_short MicroRNA-1205 Regulation of FRYL in Prostate Cancer
title_sort microrna-1205 regulation of fryl in prostate cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354587/
https://www.ncbi.nlm.nih.gov/pubmed/34386489
http://dx.doi.org/10.3389/fcell.2021.647485
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