Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [CT26 IMC RNA-seq]

ABSTRACT: In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [CT26 IMC RNA-seq]

PROVIDER: PRJNA800352 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions

Project description:Functional genomic screen in 2D cell culture is limited in identifying therapeutic targets that modulates tumor-microenvironment interaction. Through comparison of targeted CRISPR-Cas9 screens in 2D cell culture and cell line derived xenografts of lung cancer A549, we identified MEN1 as the top hit that confers differential essentialities in vitro and in vivo. Knockout of MEN1 in multiple solid cancer types does not impact cell proliferation in vitro, but significantly promotes and inhibits tumor growth in immunodeficient and immunocompetent mice, respectively. Mechanistically, knockout of MEN1 leads to redistribution of its interaction partner MLL1, a histone methyltransferase, to repetitive genomic regions that produce double stranded RNA. This resulted in MARV and cGAS-STING dependent activation of viral mimicry response, which induces tumor promoting neutrophil and tumor suppressing CD8+ T cell infiltrations in immunodeficient and immunocompetent mice, respectively. Consistently, multiple immune cell infiltrations are negatively correlated with MEN1 abundance and positively correlated with that of MLL1 in patient tumors of a broad range of cancer types. Pharmacological inhibition of MEN1-MLL1 interaction reduces tumor growth in CD8+ T cell dependent manner, and synergizes with anti-PD-L1 treatment. These findings reveal tumor microenvironment dependent oncogenic and tumor suppressive function of MEN1 and provide rationale for therapeutic targeting of MEN1 alone or in combination with immunotherapy in multiple solid cancer types.

2024-06-30 | GSE197595 | GEO

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [A549 RNA-seq]

Project description:In this study, we used a targeted CRISPR/Cas9 screen to identify genes that determine growth of A549 cells in vivo and in vitro. Functional genomic screens in 2D cell culture are of limited use for identifying therapeutic targets that modulate tumor cell-microenvironment cell interactions. By comparing targeted CRISPR-Cas9 screens in 2D culture of A549 lung cancer cells versus xenografts derived from the same cell line, we identified MEN1 as the top hit that confers differential effects in vitro and in vivo. Knockout of MEN1 in multiple solid cancer types does not impact cell proliferation in vitro, but significantly promotes or inhibits tumor growth in immunodeficient or immunocompetent mice, respectively. Mechanistically, knockout of MEN1 leads to increased chromatin interaction of its interaction partner MLL1 (KMT2A), a histone methyltransferase, to repetitive genomic regions, where it activates expression of double-stranded RNA. This results in MARV and cGAS-STING dependent activation of viral mimicry response, which induces infiltration of neutrophils and CD8+ T cells in immunodeficient and immunocompetent mice respectively. Consistently, multiple immune cell infiltrations are negatively correlated with MEN1 abundance and positively correlated with that of MLL1 in patient tumors of a broad range of cancer types. Pharmacological inhibition of MEN1-MLL interaction reduces tumor growth in CD8+ T cell dependent manner, with enhanced activity in combination with anti-PD-1 treatment. These findings reveal tumor microenvironment dependent oncogenic and tumor suppressive functions of MEN1 and provide rationale for therapeutic targeting of MEN1 alone or in combination with immunotherapy in multiple solid cancer types.

2022-11-03 | GSE194350 | GEO

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions.

Project description:In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions.

| PRJNA800345 | ENA

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions

Project description:In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions

| PRJNA811139 | ENA

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [CRISPR screening]

Project description:In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [CRISPR screening]

| PRJNA800355 | ENA

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [ChIP-seq]

Project description:In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [ChIP-seq]

| PRJNA800350 | ENA

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [CUT & RUN]

Project description:In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [CUT & RUN]

| PRJNA800351 | ENA

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [A549 RNA-seq]

Project description:In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [A549 RNA-seq]

| PRJNA800354 | ENA

In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor-microenvironment interactions [CT26 IMC RNA-seq]

Project description:In this study, we used a targeted CRISPR/Cas9 screen to identify genes that determine growth of A549 cells in vivo and in vitro.

2024-08-01 | GSE194352 | GEO

Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis

Project description:Multiple endocrine neoplasia type 1 (MEN1) syndrome is the result of mutations in the MEN1 gene and results in tumor formation via mechanisms that are not well understood. Using a novel genome-wide methylation analysis, we studied tissues from patients with MEN1-parathyroid tumors, tissues from Men1 knockout (KO) mouse models, and mouse Men1 null mouse embryonic fibroblast (MEF) cell lines. Tissues from KO mice were used to confirm and assess the findings from the MEN1 clinical samples and further explore the molecular mechanisms of global epigenetic changes following the inactivation of menin. We demonstrated that the inactivation of menin results in enhanced activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) by retinoblastoma-binding protein 5 (Rbbp5) activation in MEN1 tumor tissues. The increased activity of DNMT1 mediated global DNA hypermethylation, which in turn resulted in aberrant activation of the Wnt/Î²-catenin signaling pathway through inactivation of Sox regulatory genes. Our study provides important insights into the possible regulatory role of menin in DNA methylation and its impact on the pathogenesis of MEN1 tumor development. Global DNA methylation in tissues from patients with MEN1-parathyroid tumors. Thirty-eight human parathyroid specimens were used: 13 sporadic (non-MEN1) parathyroid adenomas, 12 MEN1-parathyroid tumors, 4 parathyroid carcinomas, and 9 normal parathyroids.

2015-12-22 | E-GEOD-64412 | biostudies-arrayexpress

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