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.
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Abbreviations
- CAHM:
-
A long non-coding RNA colorectal adenocarcinoma hypermethylated
- LncRNAs:
-
Long non-coding RNAs
- DNMT1:
-
DNA methyltransferase1
- 5-Aza:
-
5-Aza-2′-deoxycytidine
- LGGs:
-
Lower-grade gliomas
- GBMs:
-
Glioblastomas
- AUC:
-
Area under the curve
- GO:
-
Gene Ontology
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This study was funded by the National Natural Science Foundation of China (Grant Nos. 81072066, 81502149).
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Xu, Y., Li, Z., Huai, T. et al. DNMT1 Mediated CAHM Repression Promotes Glioma Invasion via SPAK/JNK Pathway. Cell Mol Neurobiol 42, 2643–2653 (2022). https://doi.org/10.1007/s10571-021-01125-z
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DOI: https://doi.org/10.1007/s10571-021-01125-z