Unveiling the Critical Role of DMRTA2-Mediated JAK2-STAT3 Pathway Activation in Glioma Prognosis and Malignant Progression

Although several studies have highlighted the significant role of DMRTA2 in several cancers, its specific function and the underlying mechanisms in glioma remain unclear. CRISPR data was leveraged to identify DMRTA2 as a key candidate. We utilized bulk-tumor, single-cell, and spatial sequencing to explore the role of DMRTA2 in glioma malignancy and its possible mechanisms. Glioma specimens were used to assess DMRTA2 expression. In vitro and in vivo experiments were performed to validate the role of DMRTA2 in glioma malignancy and its possible mechanisms. Drug prediction and molecular docking were also conducted. We found that DMRTA2 was markedly upregulated and was identified as an independent prognostic marker. Moreover, single-cell and spatial sequencing analysis demonstrated that DMRTA2 was mainly localized in glioma cells. We constructed a malignant regulatory network for DMRTA2, with the JAK-STAT pathway as a central bridge. In vitro and in vivo experiments confirmed that DMRTA2 promoted the malignant behavior of glioma cells by activating the JAK2-STAT3 pathway. Additionally, DMRTA2 was significantly correlated with genomic mutation. Drugs potentially targeting DMRTA2 were screened and docked to DMRTA2. Taken together, DMRTA2 promotes the malignant progression of gliomas by activating the JAK2-STAT3 pathway and serves as a prognostic marker.