FOXP3 promote the progression of glioblastoma via inhibiting ferroptosis mediated by linc00857/miR-1290/GPX4 axis

Abstract

The oncogenic properties of members belonging to the forkhead box (FOX) family have been extensively documented in different types of cancers. In this study, our objective was to investigate the impact of FOXP3 on glioblastoma multiforme (GBM) cells. By conducting a screen using a small hairpin RNA (shRNA) library, we discovered a significant association between FOXP3 and ferroptosis in GBM cells. Furthermore, we observed elevated levels of FOXP3 in both GBM tissues and cell lines, which correlated with a poorer prognosis. FOXP3 was found to promote the proliferation of GBM cells by inhibiting cell ferroptosis in vitro and in vivo. Mechanistically, FOXP3 not only directly upregulated the transcription of GPX4, but also attenuated the degradation of GPX4 mRNA through the linc00857/miR-1290 axis, thereby suppressing ferroptosis and promoting proliferation. Additionally, the FOXP3 inhibitor epirubicin exhibited the ability to impede proliferation and induce ferroptosis in GBM cells both in vitro and in vivo. In summary, our study provided evidences that FOXP3 facilitates the progression of glioblastoma by inhibiting ferroptosis via the linc00857/miR-1290/GPX4 axis, highlighting FOXP3 as a potential therapeutic target for GBM.

Exploring Differentially Expressed Sperm miRNAs in Idiopathic Recurrent Pregnancy Loss and Their Association with Early Embryonic Development

“…Among these DEMs, hsa-miR-1290, hsa-miR-145-5p, and hsa-miR-7977 have been previously identified as having a significant role in semen quality. Cao et al reported that FOXP3 activates the transcription of linc00857, which in turn increases the GPX4 mRNA stability via sponging hsa-miR-1290, thereby inhibiting ferroptosis [ 39 ]. On searching miRWalk, it was found that GPX4 is a gene target of hsa-miR-1290 (score = 0.846).…”