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miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer

Recent studies have shown that the downregulation of miR-145-5p in prostate cancer (PCa) is significantly associated with poor differentiation and prognosis. We aimed to investigate the biological role of miR-145-5p in the neuroendocrine differentiation (NED) of PCa. In this study, TheCancer Genome...

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Detalles Bibliográficos
Autores principales: Ji, Shuya, Shi, Yi, Yang, Lin, Zhang, Feng, Li, Yong, Xu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965462/
https://www.ncbi.nlm.nih.gov/pubmed/35368699
http://dx.doi.org/10.3389/fgene.2022.790621
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author Ji, Shuya
Shi, Yi
Yang, Lin
Zhang, Feng
Li, Yong
Xu, Feng
author_facet Ji, Shuya
Shi, Yi
Yang, Lin
Zhang, Feng
Li, Yong
Xu, Feng
author_sort Ji, Shuya
collection PubMed
description Recent studies have shown that the downregulation of miR-145-5p in prostate cancer (PCa) is significantly associated with poor differentiation and prognosis. We aimed to investigate the biological role of miR-145-5p in the neuroendocrine differentiation (NED) of PCa. In this study, TheCancer Genome Atlas was used to identify the association of miR-145-5p with PCa. The functions of miR-145-5p were evaluated using the Cell Counting Kit-8 (CCK-8) assay and cell cycle analysis. We validated changes in cell cycle control by testing the expression of cyclin-related genes by western blot. The luciferase reporter assay was performed to test miR-145-5p-targeting genes and direct transcriptional targets of SOX11. The expression of miR-145-5p was found to be significantly downregulated in castration-resistant PCa, and this was correlated with higher Gleason score and prostate-specific antigen. We confirmed these results using PC3 and LNCaP cell lines depicted a gradual decline of miR-145-5p while the cells were cultured under androgen depletion conditions. Moreover, the knockdown of miR-145-5p significantly promoted NED and proliferation of LNCaP cells, whereas overexpression of miR-145-5p significantly inhibited NED and proliferation of LNCaP cells. Mechanistically, we found that SOX11 was a direct target of miR-145-5p, which regulates MYCN might mediate induction of NED and proliferation of LNCaP cells. Furthermore, knockdown of miR-145-5p promoted tumor growth in vivo. Our findings suggest that miR-145-5p can inhibit NED and tumor growth by targeting SOX11, which regulates the expression of MYCN, and that this could be a novel therapeutic strategy for preventing the progression of PCa.
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spelling pubmed-89654622022-03-31 miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer Ji, Shuya Shi, Yi Yang, Lin Zhang, Feng Li, Yong Xu, Feng Front Genet Genetics Recent studies have shown that the downregulation of miR-145-5p in prostate cancer (PCa) is significantly associated with poor differentiation and prognosis. We aimed to investigate the biological role of miR-145-5p in the neuroendocrine differentiation (NED) of PCa. In this study, TheCancer Genome Atlas was used to identify the association of miR-145-5p with PCa. The functions of miR-145-5p were evaluated using the Cell Counting Kit-8 (CCK-8) assay and cell cycle analysis. We validated changes in cell cycle control by testing the expression of cyclin-related genes by western blot. The luciferase reporter assay was performed to test miR-145-5p-targeting genes and direct transcriptional targets of SOX11. The expression of miR-145-5p was found to be significantly downregulated in castration-resistant PCa, and this was correlated with higher Gleason score and prostate-specific antigen. We confirmed these results using PC3 and LNCaP cell lines depicted a gradual decline of miR-145-5p while the cells were cultured under androgen depletion conditions. Moreover, the knockdown of miR-145-5p significantly promoted NED and proliferation of LNCaP cells, whereas overexpression of miR-145-5p significantly inhibited NED and proliferation of LNCaP cells. Mechanistically, we found that SOX11 was a direct target of miR-145-5p, which regulates MYCN might mediate induction of NED and proliferation of LNCaP cells. Furthermore, knockdown of miR-145-5p promoted tumor growth in vivo. Our findings suggest that miR-145-5p can inhibit NED and tumor growth by targeting SOX11, which regulates the expression of MYCN, and that this could be a novel therapeutic strategy for preventing the progression of PCa. Frontiers Media S.A. 2022-03-09 /pmc/articles/PMC8965462/ /pubmed/35368699 http://dx.doi.org/10.3389/fgene.2022.790621 Text en Copyright © 2022 Ji, Shi, Yang, Zhang, Li and Xu. 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 Genetics
Ji, Shuya
Shi, Yi
Yang, Lin
Zhang, Feng
Li, Yong
Xu, Feng
miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer
title miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer
title_full miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer
title_fullStr miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer
title_full_unstemmed miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer
title_short miR-145-5p Inhibits Neuroendocrine Differentiation and Tumor Growth by Regulating the SOX11/MYCN Axis in Prostate cancer
title_sort mir-145-5p inhibits neuroendocrine differentiation and tumor growth by regulating the sox11/mycn axis in prostate cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965462/
https://www.ncbi.nlm.nih.gov/pubmed/35368699
http://dx.doi.org/10.3389/fgene.2022.790621
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