TIFA enhances glycolysis through E2F1 and promotes the progression of glioma

Cell Signal. 2024 Oct 29:125:111498. doi: 10.1016/j.cellsig.2024.111498. Online ahead of print.

Abstract

Objective: TRAF interacting protein with forkhead associated domain (TIFA) influence progression of many cancers. However, its role in glioma remains to be explored. This study investigated the function of TIFA in glioma.

Methods: The TIFA expression in glioma and patient outcomes were analyzed using online database. Gene set enrichment analysis (GSEA) revealed related mechanisms of TIFA in glioma. TIFA's effects on glioma glycolysis and growth were assessed using in vitro and in vivo experiments. Moreover, luciferase reporter and ChIP were employed to explore the interactions among E2F1, GLUT1, HK2, and LDHA. The subcutaneous xenograft assay further elaborated the effects of TIFA in glioma.

Results: We found overexpressed TIFA in glioma. Moreover, the high TIFA expression was associated with poor prognosis of glioma. Furthermore, GSEA indicated that overexpressed TIFA promoted E2F1 and glycolysis. Knockdown of TIFA decreased glioma development in cell and mice. TIFA knockdown down-regulated the expression of E2F1, GLUT1, HK2, and LDHA.

Conclusions: The study provides evidence that TIFA regulates E2F1 expression in glioma cells and promotes the proliferation, migration, and glycolysis. TIFA might be an advantageous therapeutic strategy against glioma.

Keywords: E2F1; Glioma; Glycolysis; TIFA.