Details

Autor(en) / Beteiligte

• Miao, Jiyu
• Zhao, Changan
• Tang, Kaijie
• Xiong, Xiaofan
• Wu, Fei
• Xue, Wanjuan
• Duan, Baojun
• Zhang, Huahua
• Jing, Xintao
• Li, Wen
• Sun, Ying
• Hou, Ni
• Huang, Chen

Titel

TDG suppresses the migration and invasion of human colon cancer cells via the DNMT3A/TIMP2 axis

Ist Teil von

• International journal of biological sciences, 2022-01, Vol.18 (6), p.2527-2539

Ort / Verlag

Australia: Ivyspring International Publisher Pty Ltd

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Colorectal cancer (CRC) is one of the most common malignant tumors with high rates of recurrence and mortality. Thymine DNA glycosylase (TDG) is a key molecule in the base excision repair pathway. Recently, increasing attention has been paid to the role of TDG in tumor development. However, the specific functions of TDG in CRC remain unclear. The biological functions of TDG and DNA methyltransferase 3 alpha (DNMT3A) in CRC were evaluated using migration and invasion assays, respectively. A tumor metastasis assay was performed in nude mice to determine the role of TDG. The interaction between TDG and DNMT3A was determined via co-immunoprecipitation (Co-IP). Chromatin immunoprecipitation analysis (ChIP) was used to predict the DNA-binding site of DNMT3A. We also performed methylation-specific PCR (MSP) to detect changes in TIMP2 methylation. TDG inhibited the migration and invasion of human colon cancer cells both and . TDG promoted the ubiquitination and degradation of DNMT3A by binding to it. Its interference with siDNMT3A also inhibits the migration and invasion of human colon cancer cells. Furthermore, the ChIP, MSP, and rescue experiments results confirmed that TDG accelerated the degradation of DNMT3A and significantly regulated the transcription and expression of TIMP2, thereby affecting the migration and invasion of human colon cancer cells. Our findings reveal that TDG inhibits the migration and invasion of human colon cancer cells through the DNMT3A-TIMP2 axis, which may be a potential therapeutic strategy for the development and treatment of CRC.