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YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [MeRIP-Seq]

ABSTRACT: YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [MeRIP-Seq]

PROVIDER: PRJNA850421 | ENA |

REPOSITORIES: ENA

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YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [MeRIP-Seq]

Project description:RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells augments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhibiting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-κB signaling; YTHDF2 in turn leads to NF-κB activation by directly binding and degrading transcripts encoding negative regulators of NF-κB signaling, resulting in an IR-YTHDF2-NF-κB circuit. Pharmacological inhibition of YTHDF2 overcomes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations.

2023-04-28 | GSE206384 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells

Project description:YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells

| PRJNA850417 | ENA

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [CITE-Seq]

2023-04-28 | GSE206381 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [RIP-Seq]

2023-04-28 | GSE206379 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [scRNA-Seq]

2023-04-28 | GSE206378 | GEO

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [RIP-Seq]

Project description:YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [RIP-Seq]

| PRJNA850412 | ENA

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [CITE-Seq]

Project description:YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [CITE-Seq]

| PRJNA850409 | ENA

YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [scRNA-Seq]

Project description:YTHDF2 inhibition potentiates radiotherapy by reprogramming suppressive myeloid cells [scRNA-Seq]

| PRJNA850413 | ENA

Effect of Ythdf2 in haematopoiesis [meRIP-seq]

Project description:The mRNA m6A reader YTHDF2 is overexpressed in human acute myeloid leukaemias. To understand the role of YTHDF2 in normal haematopoiesis and ageing, we performed SMART-seq on haematopoietic stem cells (HSCs) derived from young and aged (1 year old) mice. In parallel, to identify transcripts likely methylated in HSCs we performed meRIP-seq analysis of c-Kit+ cells.

2020-10-29 | GSE142020 | GEO

MeRIP, RIP and RNA Sequencing of the H1299 stable cell lines which the endogenous YTHDF2 was silenced by a short hairpin RNA targeting YTHDF2 3’UTR (shYTHDF2) and then re-expressed Flag-tagged YTHDF2-WT orYTHDF2-K571R

Project description:SUMOylation affects many aspects of target proteins such as activity, stability, localization and protein-protein interactions. We have found that SUMOylation of YTHDF2 increased its binding activity with m6A-RNAs by using different experimental approaches. To confiremd this conclusion,the analysis of RIP-seq, MeRIP-seq and RNA-seq in H1299-shYTHDF2 cells re-expressing YTHDF2-WT and YTHDF2-K571R was performed. MeRIP+RIP targets showed lower binding affinities in the mutant YTHDF2-K571R when compared with YTHDF2-WT. Compared to the control group, the binding capacities of YTHDF2 to RIP targets in treated group with either 2-D08 or GA were decreased, especially to MeRIP+RIP targets. Moreover, SUMOylated YTHDF2 promoted m6A-RNAs degradation. Combined analysis of RNA-seq, RIP-seq and MeRIP-seq showed that the mRNA levels were up-regulated in shYTHDF2 stable cells re-expressing YTHDF2-K571R compared with those in re-expressing YTHDF2-WT.

2021-01-26 | GSE164917 | GEO

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