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The study identified the E3 ligase MAEA as being expressed aberrantly in recurrent glioblastoma (GBM) samples. High expression of MAEA was associated with recurrence and poor prognosis, and functional studies showed that MAEA promoted proliferation, invasion, stemness, and resistance to temozolomide (TMZ). Mechanistically, MAEA targeted prolyl hydroxylase domain 3 (PHD3) K159 to promote its degradation, enhancing the stability of HIF-1α and promoting the stemness and TMZ resistance of GBM cells by upregulating CD133. Knocking down MAEA inhibited the growth of GBM xenograft tumors. Overall, MAEA enhances the expression of HIF-1α/CD133 through the degradation of PHD3 and promotes the malignant progression of GBM.
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