YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer

Molecular Cancer, Год журнала: 2020, Номер 19(1)

Опубликована: Окт. 29, 2020

N6-methyladenosine (m6A) is the most abundant modification in mRNA of humans. Emerging evidence has supported fact that m6A comprehensively involved various diseases especially cancers. As a crucial reader, YTHDF2 usually mediates degradation m6A-modified mRNAs m6A-dependent way. However, function and mechanisms prostate cancer (PCa) still remain elusive.To investigate functions PCa, vitro, vivo biofunctional assays epigenetics experiments were performed. Endogenous expression silencing METTL3 was established with lentivirus-based shRNA technique. Colony formation, flow cytometry trans-well performed for cell identifications. Subcutaneous xenografts metastatic mice models combined imaging system to phenotypes when knocking down METTL3. RNA immunoprecipitation (MeRIP) sequencing, RIP-RT-qPCR bioinformatics analysis mainly used screen validate direct common targets In addition, TCGA database also analyze pattern YTHDF2, target LHPP their correlation clinical prognosis.The upregulated PCa predicted worse overall survival rate. Knocking or markedly inhibited proliferation migration vitro. NKX3-1 identified as both directly bound sites mediate degradation. Knock-down significantly induced at protein level phosphorylated AKT. Overexpression presented consistent AKT phosphorylation inhibition knock-down Phosphorylated consequently confirmed downstream METTL3/YTHDF2/LHPP/NKX3-1 induce tumor migration.We propose novel regulatory mechanism which suppressors way regulate phosphorylation-induced progression cancer. We hope our findings may provide new concepts biology.

Язык: Английский

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The Biogenesis and Precise Control of RNA m6A Methylation

Trends in Genetics, Год журнала: 2019, Номер 36(1), С. 44 - 52

Опубликована: Дек. 4, 2019

Язык: Английский

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METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis

Nature Cell Biology, Год журнала: 2022, Номер 24(2), С. 205 - 216

Опубликована: Фев. 1, 2022

Язык: Английский

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N6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I

Nature Microbiology, Год журнала: 2020, Номер 5(4), С. 584 - 598

Опубликована: Фев. 3, 2020

Язык: Английский

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N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2

Nature Genetics, Год журнала: 2020, Номер 52(9), С. 870 - 877

Опубликована: Авг. 10, 2020

Язык: Английский

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