FOXM1/CENPI axis regulation of proline and arginine metabolism in glioblastoma cells

Glioblastomas (GBMs) are common malignant brain tumors that currently lack effective therapies. Therefore, exploring potential molecular regulatory mechanisms is crucial for developing new treatment strategies. Centromeric protein I (CENPI) is a member of the centromere protein family that affects the development of various cancers. Using the TCGA, we found that CENPI was significantly overexpressed in GBMs. CENPI knockdown repressed the proliferation, migration, and invasion ability of GBM cells in vitro. Gene enrichment analysis (GSEA) demonstrated that CENPI was enriched in arginine (Arg) and proline (Pro) metabolic pathways; CENPI knockdown inhibited the metabolism of these two amino acids in GBM cells. Through JASPAR prediction, dual luciferase and ChIP detection, FOXM1 was confirmed as a key transcriptional activator of CENPI. FOXM1 knockdown also depressed Arg and Pro metabolism in GBM cells thereby reducing their malignant phenotype whereas CENPI overexpression or exogenous addition of L-Arg and L-Pro restored the pro-cancer trend induced by FOXM1. Additional experiments demonstrated that the FOXM1/CENPI axis regulated the metabolism of Pro and Arg to promote GBM malignant progression modelled in vitro. In summary, our research indicated that FOXM1/CENPI signaling enhances the proliferation, migration, and invasion of GBM cells by promoting the metabolism of Arg and Pro.