Home Neoplasma 2022 Neoplasma Vol.69, No.6, p. 1373–1385, 2022

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ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.69, No.6, p. 1373–1385, 2022

Title: SUMO1-modified DNA methyltransferase 1 induces DNA hypermethylation of VWC2 in the development of colorectal cancer
Author: Xiao-Hu Cheng, Tong-Tong Xu, Lian-Bang Zhou, Fang-Yuan Li, Song Wang, Huan-Ru Liang, Jing-Jing Tang, Chang-Qin Duan, Heng Jiang, Ying-Feng Zhang, Zhi-Ning Liu

Abstract: Aberrant DNA methylation of genes is closely linked to many aspects of tumor development. This study focuses on the effect of DNA hypermethylation of von Willebrand factor C domain containing 2 (VWC2) on colorectal cancer (CRC) progression and the underpinning mechanism. According to data in the bioinformatic systems, VWC2 had the highest degree of DNA methylation in colonic adenocarcinoma, and it showed DNA hypermethylation in rectal adenocarcinoma as well. CRC and the para-tumorous tissues were collected from 86 patients. VWC2 was expressed at low levels in CRC samples and inversely correlated with tumor stage and tumor biomarker expression. DNA hypermethylation and reduced expression of VWC2 were also detected in CRC HCT-116 and HT29 cells. VWC2 overexpression suppressed the malignant growth of cells in vitro and in vivo. Co-immunoprecipitation and western blot assays showed that small ubiquitin-like modifier 1 (SUMO1) mediated SUMOylation of DNA methyltransferase 1 (DNMT1) and strengthened its protein stability, which promoted DNA methylation and suppression of the VWC2 gene. In summary, this study demonstrates that SUMO1-mediated activation of DNMT1 induces DNA methylation and downregulation of VWC2 in CRC to augment cancer development.

Keywords: SUMO1; DNMT1; VWC2; DNA methylation; colorectal cancer
Published online: 10-Nov-2022
Year: 2022, Volume: 69, Issue: 6 Page From: 1373, Page To: 1385

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