Elevated GIGYF2 expression suppresses tumor migration and enhances sensitivity to temozolomide in malignant glioma

• Published in: Cancer gene therapy 2022-06, Vol.29 (6), p.750-757
• Main Authors: Yang, Wanchun, Yuan, Qiuyun, Zhang, Shuxin, Zuo, Mingrong, Li, Tengfei, Li, Junhong, Zhou, Xingwang, Li, Mao, Feng, Wentao, Xia, Xiaoqiang, Chen, Mina, Liu, Yanhui
• Format: Article
• Language: English
• Subjects: 13/1; 13/2; 13/95; 631/67/1922; 631/80; 82/80; AKT protein; Biomedical and Life Sciences; Biomedicine; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain tumors; Carrier Proteins - genetics; Carrier Proteins - metabolism; Caspase-3; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation; Gelatinase B; Gene Expression; Gene Therapy; Glioma; Glioma - drug therapy; Glioma - genetics; Glioma - metabolism; Glioma cells; Humans; Malignancy; Neurodegeneration; Signal Transduction; Temozolomide; Temozolomide - pharmacology
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/s41417-021-00353-1

Glioma is a common type of malignant and aggressive tumor in the brain. Despite progress on mechanistic studies, current understanding of the initiation and progression of glioma remains incomplete. GIGYF2 is a critical regulator in neural development and degeneration, however, its contribution in glioma is not yet elucidated. In this study, using an integrative approach spanning bioinformatic analysis and functional approaches, we explored the potential contribution of GIGYF2 in glioma. Bioinformatic data from public database and our cohort showed that GIGYF2 expression was closely associated with low glioma malignancy and better patient survival. Elevation of GIGYF2 expression impaired cell migration and enhanced temozolomide sensitivity of human glioma cells. We further establish its molecular mechanism by demonstrating that GIGYF2 inhibits MMP-9 mediated cell migration pathway and pro-survival AKT/Bax/Caspase-3 signaling. Our work identifies the suppressive role of GIGYF2 in gliomas, and clarifies the relationship between GIGYF2 expression and glioma malignancy, which may provide a potential target for future interventions.