The Ubiquitin Hydrolase OTUB1 Promotes Glioma Cell Stemness Via Suppressing Ferroptosis Through Stabilizing SLC7A11 Protein

Overview

Journal Bioengineered

Date 2021 Dec 20

PMID 34927544

Citations 25

Authors

Xinde Zhao

Ming Zhou

Yong Yang

Minjie Luo

Affiliations

Soon will be listed here.

Abstract

The ubiquitin hydrolase OTUB1 has been elucidated to be highly expressed in tumors, however, its roles in glioma progression are still confusing. Here, via analyzing several online datasets, OTUB1 expression was shown to be remarkably increased in glioma tissues compared to that in the adjacent tissues, and predicted a poor overall survival of glioma patients. Then OTUB1 was knocked down in glioma cells and it was found that OTUB1 knockdown significantly reduced glioma cell stemness by detecting sphere-formation ability, stemness marker expression, and ALDH activity. Mechanistic experiments revealed that OTUB1 stabilized SLC7A11 protein via directly interacting with SLC7A11, which is a key suppressor of ferripotosis. Indeed, OTUB1 knockdown triggered ferroptosis dependent on SLC7A11 expression. Notably, ectopic expression of SLC7A11 attenuated the inhibition of OTUB1 knockdown on the stemenss of glioma cells. Finally, we found a positive correlation between OTUB1 and SLC7A11 expression in clinical samples. Taken together, this work identifies a novel OTUB1/SLC7A11 axis contributing to glioma cell stemness.

Citing Articles

The Role and Mechanisms of Ubiquitin-Proteasome System-Mediated Ferroptosis in Neurological Disorders.

Liu X, Wang W, Nie Q, Liu X, Sun L, Ma Q Neurosci Bull. 2025; .

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OTUB1 regulation of ferroptosis and the protective role of ferrostatin-1 in lupus nephritis.

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Therapeutic effects of natural compounds against diabetic complications via targeted modulation of ferroptosis.

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Targeting ferroptosis opens new avenues in gliomas.

Wei Y, Xu Y, Sun Q, Hong Y, Liang S, Jiang H Int J Biol Sci. 2024; 20(12):4674-4690.

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OTUB1 Promotes Glioblastoma Growth by Inhibiting the JAK2/STAT1 Signaling Pathway.

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