Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1

BackgroundExosomes have been identified to mediate the transmission of RNAs among different cells in tumor microenvironment, thus affecting the progression of different diseases. However, exosomal messenger RNAs (mRNAs) have been rarely explored. RNF157 mRNA has been found to be up-regulated in PCa...

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Main Authors: Han Guan, Likai Mao, Jinfeng Wang, Sheng Wang, Shuai Yang, Hongliang Wu, Wenyan Sun, Zhijun Chen, Ming Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.1021270/full
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author Han Guan
Likai Mao
Jinfeng Wang
Sheng Wang
Shuai Yang
Hongliang Wu
Wenyan Sun
Zhijun Chen
Ming Chen
author_facet Han Guan
Likai Mao
Jinfeng Wang
Sheng Wang
Shuai Yang
Hongliang Wu
Wenyan Sun
Zhijun Chen
Ming Chen
author_sort Han Guan
collection DOAJ
description BackgroundExosomes have been identified to mediate the transmission of RNAs among different cells in tumor microenvironment, thus affecting the progression of different diseases. However, exosomal messenger RNAs (mRNAs) have been rarely explored. RNF157 mRNA has been found to be up-regulated in PCa patients’ exosomes, but the role of exosomal RNF157 mRNA in PCa development remains unclear.MethodsOnline databases were utilized for predicting gene expression and binding correlation between different factors. RT-qPCR and western blot assays were respectively done to analyze RNA and protein expressions. Flow cytometry analysis was implemented to analyze M2 polarization.ResultsRNF157 expression was high in PCa tissues and cells. M2 polarization of macrophages was enhanced after co-culture with PCa cells or with exosomes released by PCa cells. Upon RNF157 knockdown in PCa cells, the extracted exosomes could not lead to the facilitated M2 polarization. Mechanistically, RNF157 could bind to HDAC1 and contribute to HDAC1 ubiquitination, which led to HDAC1 degradation and resulting in promoting M2 polarization of macrophages. Animal experiments validated that exosomal RNF157 accelerated PCa tumor growth through facilitating macrophage M2 polarization.ConclusionExosome-mediated RNF157 mRNA from PCa cells results in M2 macrophage polarization via destabilizing HDAC1, consequently promoting PCa tumor progression.
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spelling doaj.art-850fc8d0d5f04c6cbd80a866d30bfc602022-12-22T02:02:59ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10212701021270Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1Han Guan0Likai Mao1Jinfeng Wang2Sheng Wang3Shuai Yang4Hongliang Wu5Wenyan Sun6Zhijun Chen7Ming Chen8Department of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, ChinaDepartment of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, ChinaDepartment of Urology, Yancheng No. 3 People’s Hospital, Yancheng, ChinaDepartment of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, ChinaDepartment of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, ChinaDepartment of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, ChinaDepartment of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, ChinaDepartment of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, ChinaDepartment of Urology, Zhongda Hospital Affiliated to Southeast University, Nanjing, ChinaBackgroundExosomes have been identified to mediate the transmission of RNAs among different cells in tumor microenvironment, thus affecting the progression of different diseases. However, exosomal messenger RNAs (mRNAs) have been rarely explored. RNF157 mRNA has been found to be up-regulated in PCa patients’ exosomes, but the role of exosomal RNF157 mRNA in PCa development remains unclear.MethodsOnline databases were utilized for predicting gene expression and binding correlation between different factors. RT-qPCR and western blot assays were respectively done to analyze RNA and protein expressions. Flow cytometry analysis was implemented to analyze M2 polarization.ResultsRNF157 expression was high in PCa tissues and cells. M2 polarization of macrophages was enhanced after co-culture with PCa cells or with exosomes released by PCa cells. Upon RNF157 knockdown in PCa cells, the extracted exosomes could not lead to the facilitated M2 polarization. Mechanistically, RNF157 could bind to HDAC1 and contribute to HDAC1 ubiquitination, which led to HDAC1 degradation and resulting in promoting M2 polarization of macrophages. Animal experiments validated that exosomal RNF157 accelerated PCa tumor growth through facilitating macrophage M2 polarization.ConclusionExosome-mediated RNF157 mRNA from PCa cells results in M2 macrophage polarization via destabilizing HDAC1, consequently promoting PCa tumor progression.https://www.frontiersin.org/articles/10.3389/fonc.2022.1021270/fullexosomal RNF157 mRNAprostate cancerM2 macrophage polarizationHDAC1ubiquitination
spellingShingle Han Guan
Likai Mao
Jinfeng Wang
Sheng Wang
Shuai Yang
Hongliang Wu
Wenyan Sun
Zhijun Chen
Ming Chen
Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1
Frontiers in Oncology
exosomal RNF157 mRNA
prostate cancer
M2 macrophage polarization
HDAC1
ubiquitination
title Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1
title_full Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1
title_fullStr Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1
title_full_unstemmed Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1
title_short Exosomal RNF157 mRNA from prostate cancer cells contributes to M2 macrophage polarization through destabilizing HDAC1
title_sort exosomal rnf157 mrna from prostate cancer cells contributes to m2 macrophage polarization through destabilizing hdac1
topic exosomal RNF157 mRNA
prostate cancer
M2 macrophage polarization
HDAC1
ubiquitination
url https://www.frontiersin.org/articles/10.3389/fonc.2022.1021270/full
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