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Background Emerging oncogenes were reportedly linked to the complicated subtypes and pathogenesis of clinical gliomas. Herein, we first comprehensively explored the potential correlation between growth‐arrest‐specific two family genes (GAS2, GAS2L1, GAS2L2, GAS2L3) and gliomas by bioinformatics analysis and cellular experiments. Methods Based on the available datasets of TCGA (The Cancer Genome Atlas), CGGA (Chinese Glioma Genome Atlas), and Oncomine databases, we performed a series of analyses, such as gene expression, survival prognosis, DNA methylation, immune infiltration, and partner enrichment. We also utilized two glioma cell lines to conduct the colony formation and wound‐healing assay. Results GAS2L3 gene was highly expressed in glioma tissues compared to normal brain tissues (p, Compared with GAS2, GAS2L1, and GAS2L2, there is a stronger correlation between GAS2L3 gene expression and glioma prognosis. DNA hypomethylation of GAS2L3 may contribute to the high expression level of GAS2L3 and the poor clinical prognosis of glioma. GAS2L3 gene is capable of influencing the proliferation and migration ability of glioma cells and may be linked to a series of immune cell infiltration or cell division‐associated events in the etiology and biology of glioma.

Members of the growth arrest–specific 2 (GAS2) protein family consist of a putative actin‐binding (CH) domain and a microtubule‐binding (GAR) domain and are considered miniversions of spectraplakins. There are four members in the GAS2 family, viz. GAS2, GAS2L1, GAS2L2 and GAS2L3. Although GAS2 is defined as a family of growth arrest–specific proteins, the significant differences in the expression patterns, interaction characteristics and biological issues or diseases among the different GAS2 family members have not been systemically reviewed to date. Therefore, we summarized the available evidence on the structures and functions of GAS2 family members. This review facilitates a comprehensive molecular understanding of the involvement of the GAS2 family members in an array of biological processes, including cytoskeleton reorganization, cell cycle, apoptosis and cancer development., The GAS2 (growth arrest–specific 2) family contains a putative actin‐binding (CH) domain and a microtubule‐binding (GAR) domain There are four members in the GAS2 protein family, namely GAS2, GAS2L1, GAS2L2 and GAS2L3. Different structural characteristics of GAS2 family members lead to the distinct ways for the binding with cytoskeletal proteins, and the modulation of crosslinking between actin and microtubule, which may be the mechanistic basis of versatile role of GAS2 family in cell cycle, apoptosis or cancer.

Mitotic spindle formation and chromosome segregation require timely separation of the two duplicated centrosomes, and this process is initiated in late G2 by centrosome disjunction. Here we report that GAS2L1, a microtubule- and actin-binding protein, associates with the proximal end of mature centrioles and participates in centriole dynamics and centrosome disjunction. GAS2L1 attaches microtubules and actin to centrosomes, and the loss of GAS2L1 inhibits centrosome disjunction in G2 and centrosome splitting induced by depletion of the centrosome linker rootletin. Conversely, GAS2L1 overexpression induces premature centrosome separation, and this activity requires GAS2L1 association with actin, microtubules, and the microtubule end-binding proteins. The centrosome-splitting effect of GAS2L1 is counterbalanced by rootletin, reflecting the opposing actions of GAS2L1 and the centrosome linker. Our work reveals a GAS2L1-mediated centriole-tethering mechanism of microtubules and actin, which provide the forces required for centrosome dynamics and separation.