Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Depletion of histone methyl transferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death

ABSTRACT: Depletion of histone methyl transferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death

PROVIDER: PRJNA542325 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Depletion of histone methyltransferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death

Project description:Background: Lung cancer is the leading cause of cancer related death worldwide. Over the past 15 years no major improvement of survival rates could be accomplished. The recently discovered histone methyltransferase KMT9 as epigenetic regulator of prostate tumor growth has now raised hopes of enabling new cancer therapies. In this study we aimed to identify the function of KMT9 in lung cancer which has remained elusive so far. Methods: We linked full transcriptome and proteome analyses of A549 lung adenocarcinoma cells using RNA-Seq and mass spectrometry with functional cell culture, real-time proliferation and flow cytometry assays. Results: KMT9 is expressed in lung cancer tissue and cell lineswith high levels of KMT9 correlating with poor patient survival. We identified 460 overlapping genes and proteins that are deregulated upon knock-down of KMT9alpha in A549 cells. These genes cluster with proliferation, cell cycle and cell death gene sets as well as with subcellular organelles in gene ontology analysis. Knock-down of KMT9alpha inhibits lung cancer cell proliferation and induces non-apoptotic cell death in A549 cells. Conclusions: The novel histone methyltransferase KMT9 is crucial for proliferation and survival of lung cancer cells harboring various mutations. Small molecule inhibitors targeting KMT9 therefore should be further examined as potential milestones in modern epigenetic lung cancer therapy.

2020-05-26 | PXD014145 | Pride

Depletion of histone methyl transferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death

Project description:The aim of the study is to identify KMT9a target genes in A549 cells

2021-12-31 | GSE131016 | GEO

Structure-guided design of a selective inhibitor of the methyltransferase KMT9 with cellular activity

Project description:Inhibition of epigenetic regulators by small molecules is an attractive strategy for cancer treatment. Recently, we characterised the role of lysine methyltransferase 9 (KMT9) in prostate, lung, and colon cancer. Our observation that the enzymatic activity was required for tumour cell proliferation identified KMT9 an attractive therapeutic target. Here, we report the development of the first-in-class, potent and selective KMT9 inhibitor (compound 4, KMI169) through structure-based drug design. KMI169 functions as a bi-substrate inhibitor targeting the SAM and substrate binding pockets of KMT9 and exhibits high potency, selectivity, and cellular target engagement. KMT9 inhibition selectively downregulates target genes involved in transcription and cell cycle regulation and impairs proliferation of tumours cells including castration- and enzalutamide-resistant prostate cancer cells. Together, KMI169 represents a valuable tool to probe cellular KMT9 functions and paves the way for the development of clinical inhibitors as therapeutic options to treat malignancies such as therapy-resistant prostate cancer.

2023-12-31 | GSE235595 | GEO

KMT9 is an actionable target in muscle-invasive bladder cancer

Project description:Novel treatment modalities are imperative for the challenging management of muscle-invasive and metastatic BC to improve patient survival rates. The recently identified lysine methyltransferase (KMT) 9, an obligate heterodimer composed of KMT9α and KMT9β, regulates the growth of various types of tumors such as prostate, lung and colon cancer. While overexpression of KMT9α was previously observed to be associated with aggressive basal-like MIBC in an analysis of patients’ tissue samples, a potential functional role of KMT9 in this type of cancer has not been investigated to date. In this study, we show that KMT9 regulates proliferation and migration of various MIBC cell lines with different genetic mutations. KMT9α depletion results in differential expression of genes involved in the regulation of the cell cycle, cell adhesion and migration. Reduced cell proliferation upon KMT9α depletion is also observed in Pten/Trp53 knockout bladder tumor organoids, which cannot be rescued with an enzymatically inactive KMT9α mutant. In accordance with the idea that the catalytic activity of KMT9 is required for the control of cellular processes in MIBC, a recently developed small molecule inhibitor of KMT9 (KMI169) also impairs cancer cell proliferation. Since KMT9α depletion also restricts the growth of xenografts in mice, our data suggest that KMT9 is an actionable novel therapeutic target for the treatment of MIBC.

2024-05-01 | GSE255344 | GEO

A methyl transferase links the circadian clock to the regulation of alternative splicing

Project description:A methyl transferase links the circadian clock to the regulation of alternative splicing

| PRJNA121225 | ENA

Depletion of histone methyltransferase KMT9 inhibits lung cancer cell proliferation by inducing non-apoptotic cell death.

Project description:BackgroundLung cancer is the leading cause of cancer related death worldwide. Over the past 15 years no major improvement of survival rates could be accomplished. The recently discovered histone methyltransferase KMT9 that acts as epigenetic regulator of prostate tumor growth has now raised hopes of enabling new cancer therapies. In this study, we aimed to identify the function of KMT9 in lung cancer.MethodsWe unraveled the KMT9 transcriptome and proteome in A549 lung adenocarcinoma cells using RNA-Seq and mass spectrometry and linked them with functional cell culture, real-time proliferation and flow cytometry assays.ResultsWe show that KMT9α and -β subunits of KMT9 are expressed in lung cancer tissue and cell lines. Importantly, high levels of KMT9α correlate with poor patient survival. We identified 460 genes that are deregulated at the RNA and protein level upon knock-down of KMT9α in A549 cells. These genes cluster with proliferation, cell cycle and cell death gene sets as well as with subcellular organelles in gene ontology analysis. Knock-down of KMT9α inhibits lung cancer cell proliferation and induces non-apoptotic cell death in A549 cells.ConclusionsThe novel histone methyltransferase KMT9 is crucial for proliferation and survival of lung cancer cells harboring various mutations. Small molecule inhibitors targeting KMT9 therefore should be further examined as potential milestones in modern epigenetic lung cancer therapy.

| S-EPMC7027090 | biostudies-literature

Intervention study of ß-hydroxy-ß-methyl butyric acid on sarcopenia in patients with colorectal cancer

Project description:Interventions: Experimental group:ß- hydroxy- ß- methyl butyrate;Control Group:No Primary outcome(s): skeletal muscle index;tumor necrosis factor-like weak apoptosis-inducing factor;peroxisome proliferator-activated receptor coactivator 1-a;growth differentiation factor 15;grip strength;pace;leg circumference Study Design: Parallel

| 2716507 | ecrin-mdr-crc

A long intergenic non-coding RNA regulates nuclear localization of DNA methyl transferase-1

Project description:A long intergenic non-coding RNA regulates nuclear localization of DNA methyl transferase-1

| PRJNA414443 | ENA

The Drosophila histone methyl-transferase SET1 coordinates multiple signaling pathways in regulating male germline stem cell maintenance and differentiation

Project description:Many cell types come from tissue-specific adult stem cells that maintain the balance between proliferation and differentiation. Here, we study how the H3K4me3 methyltransferase, Set1, regulates early-stage male germ cell proliferation and differentiation in Drosophila. Early-stage germline-specific knockdown of set1 results in a temporally progressed defects, arising as germ cell loss and developing to overpopulated early-stage germ cells. These germline defects also impact the niche architecture and cyst stem cell lineage in a non-cell-autonomous manner. Additionally, wild-type Set1, but not the catalytically inactive Set1, could rescue the set1 knockdown phenotypes, highlighting the functional importance of the methyl-transferase activity of the Set1 enzyme. Further, RNA-seq experiments reveal key signaling pathway components, such as the JAK-STAT pathway gene stat92E and the BMP pathway gene mad, that are upregulated upon set1 knockdown. Genetic interaction assays support the functional relationships between set1 and JAK-STAT or BMP pathways, as mutations of both the stat92E and mad genes suppress the set1 knockdown phenotypes. These findings enhance our understanding of the balance between proliferation and differentiation in an adult stem cell lineage. The germ cell loss followed by over-proliferation phenotypes when inhibiting a histone methyl-transferase raise concerns about using their inhibitors in cancer therapy.

2024-07-31 | GSE254876 | GEO

Catechol-O-methyl transferase suppresses cell invasion and interplays with MET signaling in estrogen dependent breast cancer

Project description:Catechol-O-methyl transferase (COMT) is involved in detoxification of catechol estrogens, playing cancer-protective role in cells producing or utilizing estrogen. Moreover, COMT suppressed migration potential of breast cancer (BC) cells. To delineate COMT role in metastasis of estrogen receptor (ER) dependent BC, we investigated the effect of COMT overexpression on invasion, transcriptome, proteome and interactome of MCF7 cells, a luminal A BC model, stably transduced with lentiviral vector carrying COMT gene (MCF7-COMT). We performed comparative gene expression analysis using data obtained from RNA-seq of COMT-overexpressing and control cells in biological duplicates.

2023-02-01 | GSE203435 | 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