MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3

MicroRNA (miR)-1246 is abnormally expressed and has pro-oncogenic functions in multiple types of cancer. In the present study, its functions in breast cancer and the underlying mechanisms were further elucidated. The clinical relevance of miR-1246 was analyzed and its expression in clinical specimen...

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Autores principales:	Yue-chu Dai, Yin Pan, Ming-ming Quan, Qi Chen, Yue Pan, Yan-yun Ruan, Jian-guo Sun
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	breast cancer miR-1246 drug resistance metastasis NFE2L3 epithelial-to-mesenchymal transition 3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/00d0608b71ad4e178d6f10bd52449bb2
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id	oai:doaj.org-article:00d0608b71ad4e178d6f10bd52449bb2
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spelling	oai:doaj.org-article:00d0608b71ad4e178d6f10bd52449bb22021-12-01T22:02:44ZMicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L32234-943X10.3389/fonc.2021.677168https://doaj.org/article/00d0608b71ad4e178d6f10bd52449bb22021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.677168/fullhttps://doaj.org/toc/2234-943XMicroRNA (miR)-1246 is abnormally expressed and has pro-oncogenic functions in multiple types of cancer. In the present study, its functions in breast cancer and the underlying mechanisms were further elucidated. The clinical relevance of miR-1246 was analyzed and its expression in clinical specimens and cell lines was examined by reverse transcription-quantitat000000ive PCR analysis. FACS was used to detect cell apoptosis and mitochondrial transmembrane potential. A Transwell system was used to detect cell migration and invasion. Luciferase assay was used to confirm the target gene of miR-1246. Xenograft and metastasis mouse models were constructed to determine the function of miR-1246 in vivo. miR-1246 was found to be negatively associated with overall survival in breast cancer. miR-1246 inhibitor could effectively increase the cytotoxicity of docetaxel (Doc) by inducing apoptosis, and impair cell migration and invasion by suppressing epithelial-to-mesenchymal transition. Nuclear factor (erythroid 2)-like factor 3 (NFE2L3) was confirmed as a new target gene of miR-1246, and its overexpression was shown to reduce drug resistance and migration of MDA-MB-231 cells. More importantly, NFE2L3-silencing attenuated the effect of miR-1246 inhibitor. Finally, the inhibition of miR-1246 effectively enhanced the cytotoxicity of Doc in xenografts and impaired breast cancer metastasis. Therefore, miR-1246 may promote drug resistance and metastasis in breast cancer by targeting NFE2L3.Yue-chu DaiYin PanMing-ming QuanQi ChenYue PanYan-yun RuanJian-guo SunJian-guo SunFrontiers Media S.A.articlebreast cancermiR-1246drug resistancemetastasisNFE2L3epithelial-to-mesenchymal transition 3Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer miR-1246 drug resistance metastasis NFE2L3 epithelial-to-mesenchymal transition 3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	breast cancer miR-1246 drug resistance metastasis NFE2L3 epithelial-to-mesenchymal transition 3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yue-chu Dai Yin Pan Ming-ming Quan Qi Chen Yue Pan Yan-yun Ruan Jian-guo Sun Jian-guo Sun MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3
description	MicroRNA (miR)-1246 is abnormally expressed and has pro-oncogenic functions in multiple types of cancer. In the present study, its functions in breast cancer and the underlying mechanisms were further elucidated. The clinical relevance of miR-1246 was analyzed and its expression in clinical specimens and cell lines was examined by reverse transcription-quantitat000000ive PCR analysis. FACS was used to detect cell apoptosis and mitochondrial transmembrane potential. A Transwell system was used to detect cell migration and invasion. Luciferase assay was used to confirm the target gene of miR-1246. Xenograft and metastasis mouse models were constructed to determine the function of miR-1246 in vivo. miR-1246 was found to be negatively associated with overall survival in breast cancer. miR-1246 inhibitor could effectively increase the cytotoxicity of docetaxel (Doc) by inducing apoptosis, and impair cell migration and invasion by suppressing epithelial-to-mesenchymal transition. Nuclear factor (erythroid 2)-like factor 3 (NFE2L3) was confirmed as a new target gene of miR-1246, and its overexpression was shown to reduce drug resistance and migration of MDA-MB-231 cells. More importantly, NFE2L3-silencing attenuated the effect of miR-1246 inhibitor. Finally, the inhibition of miR-1246 effectively enhanced the cytotoxicity of Doc in xenografts and impaired breast cancer metastasis. Therefore, miR-1246 may promote drug resistance and metastasis in breast cancer by targeting NFE2L3.
format	article
author	Yue-chu Dai Yin Pan Ming-ming Quan Qi Chen Yue Pan Yan-yun Ruan Jian-guo Sun Jian-guo Sun
author_facet	Yue-chu Dai Yin Pan Ming-ming Quan Qi Chen Yue Pan Yan-yun Ruan Jian-guo Sun Jian-guo Sun
author_sort	Yue-chu Dai
title	MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3
title_short	MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3
title_full	MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3
title_fullStr	MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3
title_full_unstemmed	MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3
title_sort	microrna-1246 mediates drug resistance and metastasis in breast cancer by targeting nfe2l3
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/00d0608b71ad4e178d6f10bd52449bb2
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MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3

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