In this study, we identified the role of the TAF15/LINC00665/MTF1(YY2)/GTSE1 axis in the malignant progression of glioma, highlighting new targets for research and molecular therapy. TAF15 and LINC00665 were downregulated in glioma tissues and cells; moreover, TAF15 overexpression enhanced the stability of LINC00665, thus inhibiting the malignant progression of glioma cells. In contrast, the transcription factors MTF1 and YY2 were upregulated in glioma cells, and their knockdown, respectively, inhibited malignant progression. Mechanistically, overexpression of LINC00665 was confirmed to destabilize MTF1 and YY2 mRNAs by interacting with STAU1. In line with this mechanism, depletion of STAU1 could rescue the MTF1 and YY2 mRNA degradation caused by LINC00665 overexpression. GTSE1 was upregulated in glioma. However, knockdown of MTF1 or YY2 decreased the mRNA and protein expression levels of GTSE1 through direct binding to its promoter region, thus repressing proliferation, migration, and invasion and promoting the apoptosis of glioma cells. A schematic of the proposed mechanisms driven by this axis is provided in Figure 8D.
