MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC

Compelling evidence has implicated the role of microRNAs (miRs or miRNAs) in lung cancer. Sirtuin-1 (SIRT1) is key contributor to the progression of non small cell lung cancer (NSCLC). This study was intended to investigate whether miR-326 affected NSCLC associated with SIRT1. miR-326 and SIRT1 expr...

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Autores principales:	Jinying Wei, Guangping Meng, Jing Wu, Ying Wang, Qiang Zhang, Ting Dong, Jin Bao, Chunyan Wang, Jie Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	mir-326 sirtuin-1 hif1α vegfa non small cell lung cancer chemotherapy resistance Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/f29034f89fe24d43bf3903b6fe4f6ec8
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spelling	oai:doaj.org-article:f29034f89fe24d43bf3903b6fe4f6ec82021-11-04T15:51:54ZMicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC2165-59792165-598710.1080/21655979.2021.1993718https://doaj.org/article/f29034f89fe24d43bf3903b6fe4f6ec82021-10-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1993718https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Compelling evidence has implicated the role of microRNAs (miRs or miRNAs) in lung cancer. Sirtuin-1 (SIRT1) is key contributor to the progression of non small cell lung cancer (NSCLC). This study was intended to investigate whether miR-326 affected NSCLC associated with SIRT1. miR-326 and SIRT1 expression in H460 cells and chemoresistant cells H460-R was measured by RT-qPCR. Dual luciferase reporter gene assay and RIP assay were used to identify and validate the relationship between miR-326 and SIRT1. Using gain- and loss-of-function approaches, we evaluated their effects on the chemoresistance of NSCLC cells. ChIP assay was used to detect binding of SIRT1 to the promoter of HIF1α gene, and the binding H3K9Ac to HIF1α, binding of H3K9Ac and HIF1α after silencing SIRT1, and binding HIF1α to VEGFA promoter. In vivo experiments were performed to validate the in vitro findings. MiR-326 expression was decreased while SIRT1 expression was increased in NSCLC cells. SIRT1 was a target of miR-326. MiR-326 inhibited the proliferation of chemotherapy-resistant NSCLC cells and promoted their apoptosis by suppressing SIRT1. In addition, SIRT1 promoted chemoresistance of NSCLC cell by elevating VEGFA expression. Through this mechanism, miR-326 reduced the chemoresistance, which was validated in vivo. Taken together, miR-326 represses SIRT1 through impeding HIF1α expression, thus hindering chemotherapy resistance in lung cancer. These findings provide an exquisite therapeutic target for NSCLC.Jinying WeiGuangping MengJing WuYing WangQiang ZhangTing DongJin BaoChunyan WangJie ZhangTaylor & Francis Grouparticlemir-326sirtuin-1hif1αvegfanon small cell lung cancerchemotherapy resistanceBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mir-326 sirtuin-1 hif1α vegfa non small cell lung cancer chemotherapy resistance Biotechnology TP248.13-248.65
spellingShingle	mir-326 sirtuin-1 hif1α vegfa non small cell lung cancer chemotherapy resistance Biotechnology TP248.13-248.65 Jinying Wei Guangping Meng Jing Wu Ying Wang Qiang Zhang Ting Dong Jin Bao Chunyan Wang Jie Zhang MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC
description	Compelling evidence has implicated the role of microRNAs (miRs or miRNAs) in lung cancer. Sirtuin-1 (SIRT1) is key contributor to the progression of non small cell lung cancer (NSCLC). This study was intended to investigate whether miR-326 affected NSCLC associated with SIRT1. miR-326 and SIRT1 expression in H460 cells and chemoresistant cells H460-R was measured by RT-qPCR. Dual luciferase reporter gene assay and RIP assay were used to identify and validate the relationship between miR-326 and SIRT1. Using gain- and loss-of-function approaches, we evaluated their effects on the chemoresistance of NSCLC cells. ChIP assay was used to detect binding of SIRT1 to the promoter of HIF1α gene, and the binding H3K9Ac to HIF1α, binding of H3K9Ac and HIF1α after silencing SIRT1, and binding HIF1α to VEGFA promoter. In vivo experiments were performed to validate the in vitro findings. MiR-326 expression was decreased while SIRT1 expression was increased in NSCLC cells. SIRT1 was a target of miR-326. MiR-326 inhibited the proliferation of chemotherapy-resistant NSCLC cells and promoted their apoptosis by suppressing SIRT1. In addition, SIRT1 promoted chemoresistance of NSCLC cell by elevating VEGFA expression. Through this mechanism, miR-326 reduced the chemoresistance, which was validated in vivo. Taken together, miR-326 represses SIRT1 through impeding HIF1α expression, thus hindering chemotherapy resistance in lung cancer. These findings provide an exquisite therapeutic target for NSCLC.
format	article
author	Jinying Wei Guangping Meng Jing Wu Ying Wang Qiang Zhang Ting Dong Jin Bao Chunyan Wang Jie Zhang
author_facet	Jinying Wei Guangping Meng Jing Wu Ying Wang Qiang Zhang Ting Dong Jin Bao Chunyan Wang Jie Zhang
author_sort	Jinying Wei
title	MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC
title_short	MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC
title_full	MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC
title_fullStr	MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC
title_full_unstemmed	MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC
title_sort	microrna-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase sirt1-mediated hif1α and elevating vegfa: roles of mir-326 in chemoresistance of nsclc
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/f29034f89fe24d43bf3903b6fe4f6ec8
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MicroRNA-326 impairs chemotherapy resistance in non small cell lung cancer by suppressing histone deacetylase SIRT1-mediated HIF1α and elevating VEGFA: Roles of miR-326 in chemoresistance of NSCLC

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