RNA-binding protein TRA2A promotes glioblastoma by mediating m6A RNA modification of IFITs to recycle p-EGFR

The RNA-binding protein Transformer 2 alpha homolog (TRA2A), previously identified as an alternative splicing factor, was reported as a crucial oncogene in recent years. However, the underlying mechanisms are poorly understood. In this study, we found that TRA2A is highly up-regulated in glioblastoma and is significantly correlated with clinical diagnosis and prognosis. We verified that TRA2A promotes the proliferation and metastasis of glioblastoma. Epitranscriptomic profiling further revealed Interferon-induced protein with tetratricopeptide repeat 1/2/3 (IFIT1/2//3) as the key RNA targets mediated by TRA2A, which further over-activates the EGFR-AKT signaling pathway by enhancing the recycling of p-EGFR. This work reveals a novel oncogenic mechanism of TRA2A in glioblastoma. Methylated RNA immunoprecipitation sequencing (meRIP-seq) for TRA2A-knockdown and control U-251 MG cells.