VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression

Recent epidemiological and preclinical evidence indicates that vitamin D3 inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D3 and identify crucial targets and regulatory mechanis...

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Autores principales:	Chaojun Zhu, Zihuan Wang, Jianqun Cai, Chunqiu Pan, Simin Lin, Yue Zhang, Yuting Chen, Mengxin Leng, Chengcheng He, Peirong Zhou, Changjie Wu, Yuxin Fang, Qingyuan Li, Aimin Li, Side Liu, Qiuhua Lai
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colorectal cancer vitamin D VDR (vitamin D receptor) network pharmacology NAT2 (N-acetyl transferase 2) Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0aef70055b384406a23076745b5dfbeb
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spelling	oai:doaj.org-article:0aef70055b384406a23076745b5dfbeb2021-11-16T07:28:03ZVDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression1663-981210.3389/fphar.2021.727704https://doaj.org/article/0aef70055b384406a23076745b5dfbeb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.727704/fullhttps://doaj.org/toc/1663-9812Recent epidemiological and preclinical evidence indicates that vitamin D3 inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D3 and identify crucial targets and regulatory mechanisms in CRC. First, we confirmed that 1,25(OH)2D3, the active form of vitamin D3, suppressed the aggressive phenotype of CRC in vitro and in vivo. Based on a network pharmacological analysis, N-acetyltransferase 2 (NAT2) was identified as a potential target of vitamin D3 against CRC. Clinical data of CRC patients from our hospital and bioinformatics analysis by online databases indicated that NAT2 was downregulated in CRC specimens and that the lower expression of NAT2 was correlated with a higher metastasis risk and lower survival rate of CRC patients. Furthermore, we found that NAT2 suppressed the proliferation and migration capacity of CRC cells, and the JAK1/STAT3 signaling pathway might be the underlying mechanism. Moreover, Western blot and immunofluorescence staining assays demonstrated that 1,25(OH)2D3 promoted NAT2 expression, and the chromatin immunoprecipitation assay indicated that the vitamin D receptor (VDR) transcriptionally regulated NAT2. These findings expand the potential uses of vitamin D3 against CRC and introduce VDR signaling via the enzyme NAT2 as a potential diagnostic and therapeutic target for CRC.Chaojun ZhuZihuan WangJianqun CaiChunqiu PanSimin LinYue ZhangYuting ChenMengxin LengChengcheng HeChengcheng HePeirong ZhouPeirong ZhouChangjie WuYuxin FangQingyuan LiAimin LiSide LiuQiuhua LaiFrontiers Media S.A.articlecolorectal cancervitamin DVDR (vitamin D receptor)network pharmacologyNAT2 (N-acetyl transferase 2)Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer vitamin D VDR (vitamin D receptor) network pharmacology NAT2 (N-acetyl transferase 2) Therapeutics. Pharmacology RM1-950
spellingShingle	colorectal cancer vitamin D VDR (vitamin D receptor) network pharmacology NAT2 (N-acetyl transferase 2) Therapeutics. Pharmacology RM1-950 Chaojun Zhu Zihuan Wang Jianqun Cai Chunqiu Pan Simin Lin Yue Zhang Yuting Chen Mengxin Leng Chengcheng He Chengcheng He Peirong Zhou Peirong Zhou Changjie Wu Yuxin Fang Qingyuan Li Aimin Li Side Liu Qiuhua Lai VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression
description	Recent epidemiological and preclinical evidence indicates that vitamin D3 inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D3 and identify crucial targets and regulatory mechanisms in CRC. First, we confirmed that 1,25(OH)2D3, the active form of vitamin D3, suppressed the aggressive phenotype of CRC in vitro and in vivo. Based on a network pharmacological analysis, N-acetyltransferase 2 (NAT2) was identified as a potential target of vitamin D3 against CRC. Clinical data of CRC patients from our hospital and bioinformatics analysis by online databases indicated that NAT2 was downregulated in CRC specimens and that the lower expression of NAT2 was correlated with a higher metastasis risk and lower survival rate of CRC patients. Furthermore, we found that NAT2 suppressed the proliferation and migration capacity of CRC cells, and the JAK1/STAT3 signaling pathway might be the underlying mechanism. Moreover, Western blot and immunofluorescence staining assays demonstrated that 1,25(OH)2D3 promoted NAT2 expression, and the chromatin immunoprecipitation assay indicated that the vitamin D receptor (VDR) transcriptionally regulated NAT2. These findings expand the potential uses of vitamin D3 against CRC and introduce VDR signaling via the enzyme NAT2 as a potential diagnostic and therapeutic target for CRC.
format	article
author	Chaojun Zhu Zihuan Wang Jianqun Cai Chunqiu Pan Simin Lin Yue Zhang Yuting Chen Mengxin Leng Chengcheng He Chengcheng He Peirong Zhou Peirong Zhou Changjie Wu Yuxin Fang Qingyuan Li Aimin Li Side Liu Qiuhua Lai
author_facet	Chaojun Zhu Zihuan Wang Jianqun Cai Chunqiu Pan Simin Lin Yue Zhang Yuting Chen Mengxin Leng Chengcheng He Chengcheng He Peirong Zhou Peirong Zhou Changjie Wu Yuxin Fang Qingyuan Li Aimin Li Side Liu Qiuhua Lai
author_sort	Chaojun Zhu
title	VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression
title_short	VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression
title_full	VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression
title_fullStr	VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression
title_full_unstemmed	VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression
title_sort	vdr signaling via the enzyme nat2 inhibits colorectal cancer progression
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0aef70055b384406a23076745b5dfbeb
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VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression

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