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Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma

Noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long ncRNAs (lncRNAs) have been shown to function as pivotal regulators in the carcinogenesis of renal cell carcinoma (RCC). However, the functions and underlying mechanisms of most ncRNAs in RCC are still elusive, and the crosstalks of differen...

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Autores principales: Zhou, Hui, Tang, Kun, Liu, Haoran, Zeng, Jin, Li, Heng, Yan, Libin, Hu, Junhui, Guan, Wei, Chen, Ke, Xu, Hua, Ye, Zhangqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506628/
https://www.ncbi.nlm.nih.gov/pubmed/31071531
http://dx.doi.org/10.1016/j.omtn.2019.04.005
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author Zhou, Hui
Tang, Kun
Liu, Haoran
Zeng, Jin
Li, Heng
Yan, Libin
Hu, Junhui
Guan, Wei
Chen, Ke
Xu, Hua
Ye, Zhangqun
author_facet Zhou, Hui
Tang, Kun
Liu, Haoran
Zeng, Jin
Li, Heng
Yan, Libin
Hu, Junhui
Guan, Wei
Chen, Ke
Xu, Hua
Ye, Zhangqun
author_sort Zhou, Hui
collection PubMed
description Noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long ncRNAs (lncRNAs) have been shown to function as pivotal regulators in the carcinogenesis of renal cell carcinoma (RCC). However, the functions and underlying mechanisms of most ncRNAs in RCC are still elusive, and the crosstalks of different layers of ncRNAs are seldom reported. Here we showed that miR-124 and maternally expressed gene 3 (MEG3) were both significantly reduced in RCC, and combined expression of miR-124 and MEG3 emerged as an independent prognostic factor in our RCC cohort. Overexpression of miR-124 or MEG3 inhibited cell proliferation, migration, and invasion in vitro, and restrained tumor growth in vivo. EZH2 knockdown induced the epigenetic silencing of miR-124 and MEG3 expression by H3K27me3. Besides, miR-124 directly targeted the TET1 transcript, and then the interaction resulted in the upregulation of MEG3. Furthermore, we demonstrated that MEG3 induced p53 protein accumulation, whereas p53 was a positive transcriptional regulator of the miR-124. In addition, tumor-suppressive PTPN11 was identified as a direct target of miR-124, as well as the MEG3- and p53-regulated gene. Our study identifies three crosstalks between miR-124 and MEG3, which provide a plausible link for these two ncRNAs in RCC. Both ncRNAs exert important antitumor effects in RCC pathogenesis and might serve as prognostic biomarkers and molecular therapeutic targets.
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spelling pubmed-65066282019-05-10 Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma Zhou, Hui Tang, Kun Liu, Haoran Zeng, Jin Li, Heng Yan, Libin Hu, Junhui Guan, Wei Chen, Ke Xu, Hua Ye, Zhangqun Mol Ther Nucleic Acids Article Noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long ncRNAs (lncRNAs) have been shown to function as pivotal regulators in the carcinogenesis of renal cell carcinoma (RCC). However, the functions and underlying mechanisms of most ncRNAs in RCC are still elusive, and the crosstalks of different layers of ncRNAs are seldom reported. Here we showed that miR-124 and maternally expressed gene 3 (MEG3) were both significantly reduced in RCC, and combined expression of miR-124 and MEG3 emerged as an independent prognostic factor in our RCC cohort. Overexpression of miR-124 or MEG3 inhibited cell proliferation, migration, and invasion in vitro, and restrained tumor growth in vivo. EZH2 knockdown induced the epigenetic silencing of miR-124 and MEG3 expression by H3K27me3. Besides, miR-124 directly targeted the TET1 transcript, and then the interaction resulted in the upregulation of MEG3. Furthermore, we demonstrated that MEG3 induced p53 protein accumulation, whereas p53 was a positive transcriptional regulator of the miR-124. In addition, tumor-suppressive PTPN11 was identified as a direct target of miR-124, as well as the MEG3- and p53-regulated gene. Our study identifies three crosstalks between miR-124 and MEG3, which provide a plausible link for these two ncRNAs in RCC. Both ncRNAs exert important antitumor effects in RCC pathogenesis and might serve as prognostic biomarkers and molecular therapeutic targets. American Society of Gene & Cell Therapy 2019-04-13 /pmc/articles/PMC6506628/ /pubmed/31071531 http://dx.doi.org/10.1016/j.omtn.2019.04.005 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhou, Hui
Tang, Kun
Liu, Haoran
Zeng, Jin
Li, Heng
Yan, Libin
Hu, Junhui
Guan, Wei
Chen, Ke
Xu, Hua
Ye, Zhangqun
Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma
title Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma
title_full Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma
title_fullStr Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma
title_full_unstemmed Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma
title_short Regulatory Network of Two Tumor-Suppressive Noncoding RNAs Interferes with the Growth and Metastasis of Renal Cell Carcinoma
title_sort regulatory network of two tumor-suppressive noncoding rnas interferes with the growth and metastasis of renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506628/
https://www.ncbi.nlm.nih.gov/pubmed/31071531
http://dx.doi.org/10.1016/j.omtn.2019.04.005
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