A Novel Oncogene and Therapeutic Target, Germ Cell-Specific Gene 2 (GSG2), Plays Complex Roles in Promoting Malignant Progression of Glioma

Background: Despite decades of advancements in glioma therapy, challenges such as drug resistance, tumor recurrence, and heterogeneous treatment responses persist, underscoring the need for novel molecular targets. Currently, little is known about the vital roles of GSG2 involved in glioma. Hence, this is the first article studying the roles of GSG2 in glioma in combination with bulk RNA-Sequencing (RNA-Seq) data mining and experi-mental validations. Methods: For bioinformatics analysis, glioma bulk RNA-seq data were mined to reveal the RNA expression levels, prognostic values, and related pathways of GSG2 in glioma. As for the experiments, Western blot and IHC staining validated the expression of GSG2 in glioma cells and tissues. CCK-8, Transwell, and wound healing assays were performed to determine the proliferative, invasive, and migratory phenotypes of glioma cells. Moreover, the GSG2 stable knockdown cell lines and the xenograft assay in nude mice were also conducted to assess the effects of GSG2 on related pathway genes in vivo and in vitro. Results: Glioma bulk RNA-seq data mining showed that the GSG2 mRNA expression levels were highly expressed in glioma tissues, as verified by Western blot and IHC staining. More-over, it is also significantly linked with a worse OS prognosis (P-values <0.05). Cox regres-sion analysis demonstrated that the prognostic value of GSG2 in glioma was independent after adjusting for these nine potential confounding factors, and GSEA revealed six GSG2-related pathways in glioma (p-values <0.05). Cellular functional experiments showed that GSG2 knockdown might potently inhibit the proliferative, invasive, and migratory pheno-types in glioma cells (p-values <0.05). Besides, it could also regulate the PI3K/AKT/mTOR, EMT, glycolysis, and cell cycle-related pathway genes in vivo and in vitro (p-values <0.05). Discussion: Bioinformatics analysis showed the mRNA expression levels and prognostic values of GSG2 in glioma tissues. Further in vivo and in vitro experiments validated the high expression of GSG2 in glioma and its potential cellular functions. All of these indicated the complex roles of the GSG2 gene in glioma. Conclusion: GSG2 could serve as an oncogene and play complex roles in glioma, making it a candidate prognostic and therapeutic target for these patients.