VDR Signaling Via the Enzyme NAT2 Inhibits Colorectal Cancer Progression

Overview

Journal Front Pharmacol

Date 2021 Dec 6

PMID 34867333

Citations 8

Authors

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

Affiliations

Soon will be listed here.

Abstract

Recent epidemiological and preclinical evidence indicates that vitamin D inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D and identify crucial targets and regulatory mechanisms in CRC. First, we confirmed that 1,25(OH)D, the active form of vitamin D, suppressed the aggressive phenotype of CRC and . Based on a network pharmacological analysis, N-acetyltransferase 2 (NAT2) was identified as a potential target of vitamin D 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)D 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 D against CRC and introduce VDR signaling via the enzyme NAT2 as a potential diagnostic and therapeutic target for CRC.

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