CAMTA1, a novel antitumor gene, regulates proliferation and the cell cycle in glioma by inhibiting AKT phosphorylation.

Abstract

Identifying biomarkers for the early diagnosis of glioma and elucidating the molecular mechanisms underlying the development of this cancer are of considerable clinical importance. Recently, studies performing microarray profiling of genes to identify distinct gene signatures reported specific subtypes with predictive and prognostic relevance. Thus, we performed deep sequencing on a total of 26 glioma tissue samples to identify the frequently mutated of oncogenes and tumor suppressors in gliomas. A total of 2306 single-nucleotide polymorphisms (SNPs) and 2010 insertion and deletion sites (indels) were found by aligning sequencing information from 26 glioma samples with sequences from the normal human gene database (GRCh37/hg19). GSEA results suggest that an underexpressed gene, calmodulin binding transcription activator 1 (CAMTA1), participates in the cell proliferation and cell cycle regulation of glioma cells. Moreover, overexpression of CAMTA1 in glioma cells notably inhibited cell growth, migration, invasion and cell cycle and enhanced temozolomide (TMZ)-induced cell apoptosis in glioma cells, while CAMTA1 overexpression decreased the ITGA5, ITGB1, p-AKT, p-FAK, and Myc protein levels, suggesting that the signaling pathways of these proteins might be involved in the cellular functions of CAMTA1 in glioma. Moreover, overexpression of CAMTA1 attenuated the growth and tumorigenesis of glioma in vivo. In summary, we identified high-frequency mutant genes in glioma and provided an experimental basis for a novel mechanism by which CAMTA1 may serve as a tumor suppressor in glioma.

• Authors: Zongze He, Chen Yang, Yunsen He, Bo Gong, Cheng Yin, Jie Feng, Longyi Chen, Jian Tang, Yong Chen
• Journal: Cellular signalling (Cell Signal) Vol. 79 Pg. 109882 (03 2021) ISSN: 1873-3913 [Electronic] England
• PMID: 33316386 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• CAMTA1 protein, human
• Calcium-Binding Proteins
• Trans-Activators
• Tumor Suppressor Proteins
• Proto-Oncogene Proteins c-akt

Topics

• Adult
• Animals
• Brain Neoplasms (genetics, metabolism)
• Calcium-Binding Proteins (genetics, metabolism)
• Cell Cycle
• Cell Line, Tumor
• Female
• Glioma (genetics, metabolism)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Middle Aged
• Phosphorylation
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Trans-Activators (genetics, metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)