TRMT10A regulates tRNA-ArgCCT m1G9 modification to generate tRNA-derived fragments influencing vasculogenic mimicry formation in glioblastoma.

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system tumor. The formation of vasculogenic mimicry (VM) in GBM is closely related to poor patient prognosis. Therefore, it is urgently necessary to explore the mechanisms that promote VM formation in GBM and identify therapeutic targets. CGGA data analysis revealed that TRMT10A expression is significantly downregulated in WHO grade IV primary glioma samples compared to grade II samples, consistent with the protein expression levels. Additionally, GBM patients with low TRMT10A expression have poorer prognoses. In human glioma cells, TRMT10A expression is significantly lower than in human astrocytes. Knockdown of TRMT10A reduces m¹G9 modification of tRNA-ArgCCT, upregulates tRF-22 expression, and promotes glioma cell proliferation, migration, invasion, and tube formation. Overexpression of tRF-22 in glioma cells significantly downregulates MXD1 expression. tRF-22 negatively regulates MXD1 expression by binding to its 3'UTR, reducing MXD1's transcriptional inhibition of HIF1A, thereby promoting glioma cell proliferation, migration, invasion, and tube formation. Overexpression of TRMT10A combined with tRF-22 inhibition significantly reduces the number of VM channels and inhibits tumor growth in xenograft models in nude mice. This study elucidates the mechanism by which TRMT10A affects VM formation in glioma and provides a novel therapeutic target for GBM.