Affordable Access

Publisher Website

DNMT1-mediated NR3C1 DNA methylation enables transcription activation of connexin40 and augments angiogenesis during colorectal cancer progression.

Authors
  • Zhai, Peng1
  • Zhang, Heng2
  • Li, Qiang3
  • Yang, Ming4
  • Guo, Yunhu4
  • Xing, Chungen5
  • 1 Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, PR China; Department of General Surgery, Fifth People's Hospital of Huai'an City, Huai'an 223300, Jiangsu, PR China. , (China)
  • 2 Department of General Surgery, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing 211200, Jiangsu, PR China. , (China)
  • 3 Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, PR China; Department of Gerneral Surgery, The Second Afilliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu, PR China. , (China)
  • 4 Department of General Surgery, Fifth People's Hospital of Huai'an City, Huai'an 223300, Jiangsu, PR China. , (China)
  • 5 Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, PR China. Electronic address: [email protected]. , (China)
Type
Published Article
Journal
Gene
Publication Date
Jan 20, 2024
Volume
892
Pages
147887–147887
Identifiers
DOI: 10.1016/j.gene.2023.147887
PMID: 37813207
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Colorectal cancer (CRC) continues to be a major contributor to cancer-related mortality. Connexin 40 (CX40) is one of the major gap junction proteins with the capacity in regulating cell-to-cell communication and angiogenesis. This study investigates its role in angiogenesis in CRC and explores the regulatory mechanism. Aberrant high CX40 expression was detected in tumor tissues, which was associated with a poor prognosis in CRC patients. Elevated CX40 expression was detected in CRC cell lines as well. Conditioned medium of SW620 and HT29 cell lines was used to induce angiogenesis of human umbilical vein endothelial cells (HUVECs). CX40 knockdown in CRC cells reduced angiogenesis and mobility of HUVECs and blocked CRC cell proliferation, mobility, and survival. Following bioinformatics predictions, we validated by chromatin immunoprecipitation and luciferase assays that nuclear receptor subfamily 3 group C member 1 (NR3C1), which was poorly expressed in CRC samples, suppressed CX40 transcription. The poor NR3C1 expression was attributive to DNA hypermethylation induced by DNA methyltransferase 1 (DNMT1). Restoration of NR3C1 suppressed the pro-angiogenic effect, proliferation and survival, and tumorigenic activity of CRC cells, which were, however, rescued by CX40 upregulation. Collectively, this study demonstrates that transcription activation of CX40 upon DNMT1-mediated NR3C1 DNA methylation potentiates angiogenesis in CRC. Copyright © 2023 Elsevier B.V. All rights reserved.

Report this publication

Statistics

Seen <100 times