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The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression
For human prostate cancer, the chromosome 8p21 locus, which contains NKX3.1 and the microRNA (miR)-3622 family (miR-3622a/b), is a frequently deleted region. Thus, miR-3622 is proposed as a suppressor for prostate cancer, but its role remains debatable. In the present study, we found that expression...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177620/ https://www.ncbi.nlm.nih.gov/pubmed/35501464 http://dx.doi.org/10.1038/s41388-022-02289-8 |
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author | Zhang, Yue Xu, Zhifang Wen, Wen Liu, Zhichao Zhang, Chao Li, Ming Hu, Fengping Wei, Shi Bae, Sejong Zhou, Jiangbing Liu, Runhua Wang, Lizhong |
author_facet | Zhang, Yue Xu, Zhifang Wen, Wen Liu, Zhichao Zhang, Chao Li, Ming Hu, Fengping Wei, Shi Bae, Sejong Zhou, Jiangbing Liu, Runhua Wang, Lizhong |
author_sort | Zhang, Yue |
collection | PubMed |
description | For human prostate cancer, the chromosome 8p21 locus, which contains NKX3.1 and the microRNA (miR)-3622 family (miR-3622a/b), is a frequently deleted region. Thus, miR-3622 is proposed as a suppressor for prostate cancer, but its role remains debatable. In the present study, we found that expression of miR-3622a was lower, whereas expression of miR-3622b-3p was higher in human prostate cancer tissues than in normal prostate tissues. miR-3622a-3p inhibited cell migration and invasion of human prostate cancer cells, whereas miR-3622b-3p facilitated cell proliferation, migration, and invasion. To address the opposing roles of miR-3622 family members in various human prostate cancer cell lines, we knocked out (KO) endogenous miR-3622, including both miR-3622a/b. Our results showed that miR-3622 KO reduced cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Functional analyses revealed that miR-3622 regulated the p53 downstream gene network, including AIFM2, c-MYC, and p21, to control apoptosis and the cell cycle. Furthermore, using CRISPR interference, miRNA/mRNA immunoprecipitation assays, and dual-luciferase assays, we established that AIFM2, a direct target of miR-3622b-3p, is responsible for miR-3622 KO-induced apoptosis. We identified an miR-3622-AIFM2 axis that contributes to oncogenic function during tumor progression. In addition, miR-3622 KO inhibited the epithelial-mesenchymal transition involved in prostate cancer metastasis via upregulation of vimentin. The results show that miR-3622b-3p is upregulated in human prostate cancers and has an oncogenic function in tumor progression and metastasis via repression of p53 signaling, especially through an miR-3622-AIFM2 axis. In contrast, for human prostate cancer, deletion of the miR-3622 locus at 8p21 reduced the oncogenic effects on tumor progression and metastasis. |
format | Online Article Text |
id | pubmed-9177620 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-91776202022-11-02 The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression Zhang, Yue Xu, Zhifang Wen, Wen Liu, Zhichao Zhang, Chao Li, Ming Hu, Fengping Wei, Shi Bae, Sejong Zhou, Jiangbing Liu, Runhua Wang, Lizhong Oncogene Article For human prostate cancer, the chromosome 8p21 locus, which contains NKX3.1 and the microRNA (miR)-3622 family (miR-3622a/b), is a frequently deleted region. Thus, miR-3622 is proposed as a suppressor for prostate cancer, but its role remains debatable. In the present study, we found that expression of miR-3622a was lower, whereas expression of miR-3622b-3p was higher in human prostate cancer tissues than in normal prostate tissues. miR-3622a-3p inhibited cell migration and invasion of human prostate cancer cells, whereas miR-3622b-3p facilitated cell proliferation, migration, and invasion. To address the opposing roles of miR-3622 family members in various human prostate cancer cell lines, we knocked out (KO) endogenous miR-3622, including both miR-3622a/b. Our results showed that miR-3622 KO reduced cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Functional analyses revealed that miR-3622 regulated the p53 downstream gene network, including AIFM2, c-MYC, and p21, to control apoptosis and the cell cycle. Furthermore, using CRISPR interference, miRNA/mRNA immunoprecipitation assays, and dual-luciferase assays, we established that AIFM2, a direct target of miR-3622b-3p, is responsible for miR-3622 KO-induced apoptosis. We identified an miR-3622-AIFM2 axis that contributes to oncogenic function during tumor progression. In addition, miR-3622 KO inhibited the epithelial-mesenchymal transition involved in prostate cancer metastasis via upregulation of vimentin. The results show that miR-3622b-3p is upregulated in human prostate cancers and has an oncogenic function in tumor progression and metastasis via repression of p53 signaling, especially through an miR-3622-AIFM2 axis. In contrast, for human prostate cancer, deletion of the miR-3622 locus at 8p21 reduced the oncogenic effects on tumor progression and metastasis. 2022-06 2022-05-02 /pmc/articles/PMC9177620/ /pubmed/35501464 http://dx.doi.org/10.1038/s41388-022-02289-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms |
spellingShingle | Article Zhang, Yue Xu, Zhifang Wen, Wen Liu, Zhichao Zhang, Chao Li, Ming Hu, Fengping Wei, Shi Bae, Sejong Zhou, Jiangbing Liu, Runhua Wang, Lizhong The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression |
title | The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression |
title_full | The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression |
title_fullStr | The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression |
title_full_unstemmed | The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression |
title_short | The microRNA-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression |
title_sort | microrna-3622 family at the 8p21 locus exerts oncogenic effects by regulating the p53-downstream gene network in prostate cancer progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177620/ https://www.ncbi.nlm.nih.gov/pubmed/35501464 http://dx.doi.org/10.1038/s41388-022-02289-8 |
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