THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression.

ABSTRACT: Glioblastoma (GBM), the most common and aggressive primary malignant brain tumor in adults, has a median survival of 14.6 months. To identify drivers of GBM pathogenesis, we conducted a CRISPR-knockout screen, which revealed THO Complex 1 (THOC1) as a key driver. Knocking down THOC1 significantly reduced GBM cell viability across patient-derived xenograft (PDX) lines, enhancing survival (p<0.01) in primary PDX models. Conversely, overexpressing THOC1 in non-cancerous neural stem cells bolstered transformation capacity, decreasing survival and causing tumor engraftment in vivo (p<0.01). Further investigation revealed THOC1's interaction with SIN3A, a histone deacetylase complex. Histone deacetylation has been previously shown to prevent the buildup of R-loops, structures that form normally

SUBMITTER: Budhiraja S 

PROVIDER: S-EPMC12808535 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature