Dataset Information

The ubiquitin hydrolase OTUB1 promotes glioma cell stemness via suppressing ferroptosis through stabilizing SLC7A11 protein.

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.

SUBMITTER: Zhao X

PROVIDER: S-EPMC8810032 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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The ubiquitin hydrolase OTUB1 promotes glioma cell stemness via suppressing ferroptosis through stabilizing SLC7A11 protein.

Zhao Xinde X Zhou Ming M Yang Yong Y Luo Minjie M

Bioengineered 20211201 2

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 ...[more]

PMID: 34927544

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Project description:BackgroundN6-methyladenosine (m6A) has emerged as a significant regulator of the progress of various cancers. However, its role in lung adenocarcinoma (LUAD) remains unclear. Here, we explored the biological function and underlying mechanism of methyltransferase-like 3 (METTL3), the main catalyst of m6A, in LUAD progression.MethodsThe expression of m6A, METTL3, YTHDF1 and SLC7A11 were detected by immunochemistry or/and online datasets in LUAD patients. The effects of METTL3 on LUAD cell proliferation, apoptosis and ferroptosis were assessed through in vitro loss-and gain-of-function experiments. The in vivo effect on tumorigenesis of METTL3 was evaluated using the LUAD cell xenograft mouse model. MeRIP-seq, RNA immunoprecipitation and RNA stability assay were conducted to explore the molecular mechanism of METTL3 in LUAD.ResultsThe results showed that the m6A level, as well as the methylase METTL3 were both significantly elevated in LUAD patients and lung cancer cells. Functionally, we found that METTL3 could promote proliferation and inhibit ferroptosis in different LUAD cell models, while METTL3 knockdown suppressed LUAD growth in cell-derived xenografts. Mechanistically, solute carrier 7A11 (SLC7A11), the subunit of system Xc-, was identified as the direct target of METTL3 by mRNA-seq and MeRIP-seq. METTL3-mediated m6A modification could stabilize SLC7A11 mRNA and promote its translation, thus promoting LUAD cell proliferation and inhibiting cell ferroptosis, a novel form of programmed cell death. Additionally, we demonstrated that YTHDF1, a m6A reader, was recruited by METTL3 to enhance SLC7A11 m6A modification. Moreover, the expression of YTHDF1 and SLC7A11 were positively correlated with METTL3 and m6A in LUAD tissues.ConclusionsThese findings reinforced the oncogenic role of METTL3 in LUAD progression and revealed its underlying correlation with cancer cell ferroptosis; these findings also indicate that METTL3 is a promising novel target in LUAD diagnosis and therapy.

Dataset Information

The ubiquitin hydrolase OTUB1 promotes glioma cell stemness via suppressing ferroptosis through stabilizing SLC7A11 protein.

Publications

The ubiquitin hydrolase OTUB1 promotes glioma cell stemness via suppressing ferroptosis through stabilizing SLC7A11 protein.

Similar Datasets

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