DNMT1 Mediated CAHM Repression Promotes Glioma Invasion via SPAK/JNK Pathway.

Abstract

Gliomas are the most common and fatal brain tumors worldwide. Abnormal DNA promoter methylation is an important mechanism for gene loss of tumor suppressors. A long non-coding RNA colorectal adenocarcinoma hypermethylated (CAHM) has been reported to be nearly deleted in glioblastomas (GBMs). Nevertheless, the roles of CAHM in gliomas remain unknown up to now. In the present study, 969 glioma samples downloaded from the CGGA and Gravendeel databases were included. We found that CAHM expression was correlated with glioma grades, molecular subtype, IDH mutation status, and 1q/19p codel status. In glioma cells, CAHM is hypermethylated by DNA methyltransferase1 (DNMT1) and the loss of CAHM expression could be reversed by 5-Aza-2'-deoxycytidine (5-Aza), a specific inhibitor of DNA methyltransferases. Besides, the expression of CAHM was negatively associated with overall survival in both primary and recurrent gliomas. Moreover, the result of Gene Ontology (GO) analysis suggested that CAHM participated in negatively regulating cell development, nervous system development, neurogenesis, and integrin-mediated signaling pathway. Overexpression of CAHM inhibited glioma cell proliferation, clone formation, and invasion. Further exploring results showed that CAHM overexpression suppressed glioma migration and invasion through SPAK/MAPK pathway. Collectively, this study disclosed that CAHM might be a suppressor in gliomas.

• Authors: Yadi Xu, Zelin Li, Tian Huai, Xiuhao Huo, Hongliang Wang, Erbao Bian, Bing Zhao
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 42 Issue 8 Pg. 2643-2653 (Nov 2022) ISSN: 1573-6830 [Electronic] United States
• PMID: 34227028 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• CAHM long non-coding RNA, human
• Integrins
• RNA, Long Noncoding
• Decitabine
• DNA
• DNA Modification Methylases
• DNA (Cytosine-5-)-Methyltransferase 1
• DNMT1 protein, human

Topics

• Adenocarcinoma (genetics)
• Brain Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics)
• DNA
• DNA (Cytosine-5-)-Methyltransferase 1
• DNA Methylation (genetics)
• DNA Modification Methylases
• Decitabine
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, pathology)
• Humans
• Integrins (genetics)
• MAP Kinase Signaling System
• RNA, Long Noncoding (genetics)