Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocyt...

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Autores principales:	Junping Wang, Cheng Huo, Jinzhu Yin, Lixia Tian, Lili Ma, Dongsheng Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	noncoding RNAs microRNA-338-5p E26 transformation-specific sequence 1 DNA methylation astrocytoma DNA methyltransferase 1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c84f3a93220b4240b9ebe7fd180327bd
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spelling	oai:doaj.org-article:c84f3a93220b4240b9ebe7fd180327bd2021-11-11T10:22:11ZHypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients2234-943X10.3389/fonc.2021.773644https://doaj.org/article/c84f3a93220b4240b9ebe7fd180327bd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.773644/fullhttps://doaj.org/toc/2234-943XThe pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.Junping WangJunping WangCheng HuoJinzhu YinLixia TianLili MaDongsheng WangFrontiers Media S.A.articlenoncoding RNAsmicroRNA-338-5pE26 transformation-specific sequence 1DNA methylationastrocytomaDNA methyltransferase 1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	noncoding RNAs microRNA-338-5p E26 transformation-specific sequence 1 DNA methylation astrocytoma DNA methyltransferase 1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	noncoding RNAs microRNA-338-5p E26 transformation-specific sequence 1 DNA methylation astrocytoma DNA methyltransferase 1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Junping Wang Junping Wang Cheng Huo Jinzhu Yin Lixia Tian Lili Ma Dongsheng Wang Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients
description	The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.
format	article
author	Junping Wang Junping Wang Cheng Huo Jinzhu Yin Lixia Tian Lili Ma Dongsheng Wang
author_facet	Junping Wang Junping Wang Cheng Huo Jinzhu Yin Lixia Tian Lili Ma Dongsheng Wang
author_sort	Junping Wang
title	Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients
title_short	Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients
title_full	Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients
title_fullStr	Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients
title_full_unstemmed	Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients
title_sort	hypermethylation of the promoter of mir-338-5p mediates aberrant expression of ets-1 and is correlated with disease severity of astrocytoma patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c84f3a93220b4240b9ebe7fd180327bd
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Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

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