Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

M6A RNA methyltransferases Mettl3/14 regulate immune responses to anti-PD-1 therapy

ABSTRACT: We analyzed the RNA-seq and MeRIP-seq data from Mettl3/14 CRISPR knock-out and control CT26 colon cancer's mouse model.

ORGANISM(S): Mus musculus

PROVIDER: GSE142589 | GEO | 2020/09/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

m6A RNA methyltransferases Mettl3/14 regulate immune responses to anti-PD-1 therapy

Project description:An impressive clinical success has been observed in treating a variety of cancers using immunotherapy with programmed cell death-1 (PD-1) checkpoint blockade. However, limited response in most patients treated with anti-PD-1 antibodies remains a challenge, requiring better understanding of molecular mechanisms limiting immunotherapy. In colorectal cancer (CRC) resistant to immunotherapy, mismatch-repair-proficient or microsatellite instability-low (pMMR-MSI-L) tumors have low mutation burden and constitute ~85% of patients. Here, we show that inhibition of N6-methyadenosine (m6A) mRNA modification by depletion of methyltransferases, Mettl3 and Mettl14, enhanced response to anti-PD-1 treatment in pMMR-MSI-L CRC and melanoma. Mettl3 or Mettl14 deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-?, Cxcl9 and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-?-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2. Finally, we found a negative correlation between METTL3 or METTL14 and STAT1 in 59 patients with pMMR-MSI-L CRC tumors. Altogether, our findings uncover a new awareness of the function of RNA methylation in adaptive immunity and provide METTL3 and METTL14 as potential therapeutic targets in anticancer immunotherapy.

| S-SCDT-EMBOJ-2020-104514 | biostudies-other

m6A RNA methyltransferases Mettl3/14 regulate immune responses to anti-PD-1 therapy

Project description:m6A RNA methyltransferases Mettl3/14 regulate immune responses to anti-PD-1 therapy

| PRJNA598869 | ENA

MeRIP-Seq (m6A-Seq) identifies the mRNA m6A modification target in negative control and METTL3 knockdwon HULEC-5a

Project description:To identify the molecular mechanism by which METTL3 regulates endothelial barrier function, we performed RNA-seq and MeRIP-seq in HULEC-5a cells with stable METTL3 knockdown and control cells. The RNA-seq results revealed that 437 transcripts were significantly downregulated (fold change <0.5) after METTL3 knockdown. The MeRIP-seq results revealed that the m6A peaks in 1011 transcripts were decreased in abundance (fold change >1.2). Intriguingly, 55 transcripts overlapped in the RNA-seq and MeRIP-seq data

2022-05-20 | GSE200648 | GEO

m<sup>6</sup> A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy.

Project description:An impressive clinical success has been observed in treating a variety of cancers using immunotherapy with programmed cell death-1 (PD-1) checkpoint blockade. However, limited response in most patients treated with anti-PD-1 antibodies remains a challenge, requiring better understanding of molecular mechanisms limiting immunotherapy. In colorectal cancer (CRC) resistant to immunotherapy, mismatch-repair-proficient or microsatellite instability-low (pMMR-MSI-L) tumors have low mutation burden and constitute ~85% of patients. Here, we show that inhibition of N6 -methyladenosine (m6 A) mRNA modification by depletion of methyltransferases, Mettl3 and Mettl14, enhanced response to anti-PD-1 treatment in pMMR-MSI-L CRC and melanoma. Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-γ, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-γ-Stat1-Irf1 signaling through stabilizing the Stat1 and Irf1 mRNA via Ythdf2. Finally, we found a negative correlation between METTL3 or METTL14 and STAT1 in 59 patients with pMMR-MSI-L CRC tumors. Altogether, our findings uncover a new awareness of the function of RNA methylation in adaptive immunity and provide METTL3 and METTL14 as potential therapeutic targets in anticancer immunotherapy.

| S-EPMC7560214 | biostudies-literature

Mettl3-mediated m6A Methylation Determines the Size of Endocrine Progenitor Pool and Postnatal Islet Mass

Project description:To investigate the role of RNA methyltransferase-like 3 (Mettl3)-mediated m6A modification in pancreatic endocrine differentiation in early embryonic period. We then performed m6A MeRIP-seq (GenSeq®️ m6A MeRIP Kit) at E15.5 Mettl3pKO pancreas group and E15.5 WT pancreas group

2023-04-16 | GSE229502 | GEO

METTL3 mediated m6A mRNA methylation regulates neutrophil activation through targeting TLR4 signaling (meRIP-Seq)

Project description:To investigate the effect of METTL3 function in the regulation of neutrophil activation, we established neutrophil METTL3 knock out mice by crossing METTL3flox/flox mice with Lyzm-cre mice. We then performed gene expression profiling analysis using data obtained from MeRIP-seq of isolated neutrophil from METTL3f/f and METTL3f/f Lyzm-Cre mice .

2023-03-31 | GSE225139 | GEO

m6A methylome in WT- and K177Q-METTL3 reconstituting MDA-MB-231 cells as well as in METTL3-deficient MDA-MB-231 cells.

Project description:We report the application of MeRIP sequencing technology for high-throughput profiling of m6A methylome in breast cancer cells. Comparison of m6A methylome between METTL3-WT and METTL3-K177Q reconstituting cells revealed the following findings: 1) Significant global alteration of methylation sites due to K177Q mutation (termed as KQ-m6A signature). 2) GO analysis of the differential m6A-MeRIP candidates enriched pathways involved in chromatin modification, RNA splicing, DNA damage, cell cycle, and autophagy, consistent with a critical role of m6A-mediated nuclear biological activities and highlighted generally recognized cellular events associated with tumorigenesis. 3) we dissected potential mechanistic clues explaining the attenuated invasive phenotype in METTL3K177Q reconstituting cells.

2022-09-20 | GSE183014 | GEO

METTL3 Facilitates Hypertrophic Scar Fibrosis by Promoting pri-miRNA-31 Maturation and ZBTB20 Silencing in m6A-dependent Manner [MeRIP-Seq]

Project description:To clarify the role of METTL3-mediated m6A modification in hypertrophic scars (HS), we conditionally knocked out the m6A methyltransferase METTL3 in HS-derived dermal fibroblasts (HSFBs). We then performed MeRIP-seq analysis on HSFBs.

2024-08-30 | GSE246978 | GEO

Mettl3 mediated m6A methylation in human bronchial epithelial cells exposed to cigarette smoke extract

Project description:To investigate the mRNA m6A modification profiling in 16-HBE cells with or without siRNA-mediated Mettl3 knockdown exposed to cigarette smoke extract, we performed m6A MeRIP-seq with the total RNA extracted from two samples.

2023-06-07 | GSE209802 | GEO

Determine the methyltransferase activities of METTL3, METTL14, and METTL16 via MeRIP-seq (m6A-seq)

Project description:All the three enzymes, METTL3, METTL14, and METTL16, belong to methyltransferase like (METTL) family and possess the ability to deposit N6-methyladenosine (m6A) in mRNA. Via immunofluorescence staining and wertern blotting, we discovered either METTL3 or METTL14 mainly localize in nuclear, but METTL16 localizes in both cytosol and nuclei. To compare the m6A methyltransferase activities of the three m6A 'writers' and better understand their differences, MeRIP-seq (m6A-seq) was conducted with poly(A) RNAs isolaed from HEK293T cells with METTL3, 14 and 16 knockout.

2021-10-28 | GSE182607 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data