SERPINI1 functions as a tumor suppressor in glioma.

Glioma is a common malignant tumor of the central nervous system associated with poor prognosis, highlighting the urgent need for novel tumor suppressors. Here, we identify SERPINI1 (a serpini family member) as a tumor suppressor in glioma, with a focus on glioblastoma (GBM). Integrative analysis of TCGA, GEO, and CGGA datasets demonstrated downregulation of SERPINI1 in glioma versus normal brain tissues, with lower SERPINI1 expression associated with higher tumor grade and worse clinical outcomes. Functional assays showed that SERPINI1 suppresses glioma cell proliferation, migration, and invasion of GBM cells. Mechanistically, IP-mass spectrometry identified 167 SERPINI1-interacting proteins, including VRK1 and VRK3, which are involved in critical oncogenic pathways. Key interactions were validated by co-IP and Western blot, as well as by immunofluorescence co-localization assays. Furthermore, structural prediction demonstrated that SERPINI1 specifically targets the catalytic domain of VRK1/VRK3, potentially modulating their activity. Our findings establish SERPINI1 as a novel tumor suppressor in GBM and highlight its regulatory network as a potential therapeutic target.