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. 2021 Nov 16;12:727704. doi: 10.3389/fphar.2021.727704

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Copyright © 2021 Zhu, Wang, Cai, Pan, Lin, Zhang, Chen, Leng, He, Zhou, Wu, Fang, Li, Li, Liu and Lai.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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VDR promotes NAT2 expression by binding to the NAT2 promoter. (A) Correlation between NAT2 and VDR mRNA expression in normal colorectal tissues and CRC tissues from GEPIA. (B,C) VDR mRNA expression was detected in 33 consecutive CRC specimens and paired adjacent normal specimens (B) and was positively correlated with NAT2 (C). (D) IHC staining in serial sections of paired CRC tissues was performed to analyze the correlation between VDR and NAT2 protein expression. Three typical cases among 19 patients with CRC are displayed. Scale bar: 50 μm. (E) RT-qPCR and Western blot assays of NAT2 in SW480 and LoVo cells transfected with the negative control or VDR overexpression plasmid. (F) Chromatin immunoprecipitation assay was used to confirm that VDR binds to the promoter region of NAT2 in SW480 cells. The immunoprecipitated DNA was quantified by RT-qPCR. (G,H) Kaplan–Meier survival curves depicting the survival of patients with CRC stratified by VDR and NAT2 mRNA expression levels [data sources: TCGA (G) and GSE17538 (H)]. Three independent experiments were performed for (E). The data are presented as mean ± SD [Spearman’s correlation analysis for (A,C); Student’s t test for (B,E,F); Log-rank test for (G,H). *, p < 0.05; **, p < 0.01; ***, p < 0.001; n.s., non-significant].