Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Overexpressed Malat1 drives metastasis through inflammatory reprogramming of lung adenocarcinoma microenvironment

ABSTRACT: Although the expression of some long noncoding RNAs (lncRNAs), including MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), is predictive of metastasis, their impact and mechanism of action remain elusive. Here we use CRISPR activation (CRISPRa) to model MALAT1/Malat1 overexpression in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. The results indicate that Malat1 overexpression alone is sufficient to enable the progression of LUAD to metastatic disease. We show that overexpressed MALAT1/Malat1 enhances cell mobility and promotes the recruitment of pro-tumor macrophages to the tumor microenvironment through paracrine secretion of the CCL2/Ccl2 cytokine. We determine that Ccl2 upregulation results from an increase in global chromatin accessibility upon Malat1 overexpression. Importantly, macrophage depletion and Ccl2 blockade counteracted the effects of Malat1 overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.

ORGANISM(S): Mus musculus

PROVIDER: GSE266561 | GEO | 2024/05/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

lncRNA MALAT1 interactome - Quantitative proteomics reveals that long non-coding RNA MALAT1 interacts with DBC1 to regulate p53 acetylation

Project description:Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that was first discovered as a prognostic marker for lung cancer metastasis. MALAT1 has been implicated in the tumorigenesis of numerous tumor types. To further delineate the underlying molecular mechanism, we established a high-throughput strategy to characterize the interacting proteins of MALAT1 by combining RNA pull down, quantitative proteomics, bioinformatics analysis, and experimental validation.

2018-10-26 | PXD005154 | Pride

Differentiation of Mammary Tumors and Reduction in Metastasis Upon Malat1 LncRNA Loss

Project description:Genome-wide analyses have identified thousands of long non-coding RNAs (lncRNAs). Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genomic loss, as well as systemic knockdown of Malat1 using antisense oligonucleotides, in the MMTV-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by differentiation into highly cystic tumors and a significant reduction in lung metastasis. Further, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT and Her2/neu amplified tumor organoids consistent with the in vivo reduction in lung metastasis. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and pro-tumorigenic signaling pathways. Together, these data indicate that the lncRNA Malat1 regulates critical processes in mammary cancer pathogenesis and represents a promising therapeutic target for inhibiting breast cancer metastasis. Transcriptome profiles of tumors and organoids after Malat1 knockdown using antisense olgonucleotides (ASOs).

2016-01-12 | E-GEOD-67647 | biostudies-arrayexpress

Differentiation of Mammary Tumors and Reduction in Metastasis Upon Malat1 LncRNA Loss

2016-01-12 | GSE67647 | GEO

Transcriptomic profiling of Lung adenocarcinoma brain metastasis

Project description:Brain metastasis developed in nearly 40% of lung adenocarcinoma (LUAD) patients diagnosed with distant metastasis. There is lack of transcriptomic data of brain lesions from human lung adenocarcinoma patients. As part of the project to understanding the tumor microenvironment in brain metastasis of LUAD patients, we performed bulk RNA analysis on brain metastases from 6 LUAD patients. In order to understand the tumor intrinsic factors that potential shape the tumor microenvironment, we compared these data with bulk RNA sequencing data from 14 early stage and 11 late stage primary LUAD tumor from TCGA database. Pathway expression analysis showed a downregulation of pro-inflammatory signals in brain metastasis and upregulation of DNA synthesis and oxidative phosphorylation pathways related to rapid proliferation in brain lesions.

2019-12-10 | GSE141685 | GEO

MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) Human HCC proteomics

Project description:The long noncoding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), also known as MALAT-1 or NEAT2 (nuclear-enriched abundant transcript 2), is a highly conserved nuclear noncoding RNA (ncRNA). Two molecular functions of MALAT1 have been proposed, one is the control of alternative splicing and the other is the transcriptional regulation. To uncover its function in HCC, we knock down it in human HCC LM3 cell lines, and profiling the sample with LC/MS/MS and RNA sequencing.

2021-09-21 | PXD016790 | Pride

Transcriptomic sequencing after MALAT1 knockdown in A431 cells

Project description:Cutaneous squamous cell carcinoma (CSCC) is the most common metastatic skin cancer, and its incidence is increasing globally. In this study, metastasis-associated in lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA, was identified to be significantly up-regulated in CSCC tumors and cell lines. We conducted RNA sequencing to characterize gene expression changes in MALAT1-silenced cutaneous squamous cell carcinoma cells (A431).

2018-06-23 | GSE100399 | GEO

Proteomic changes between primary tumors and matched distant metastases of lung adenocarcinomas

Project description:Lung cancer is the leading cause of cancer-related deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD are still insufficiently understood. Prognosis for lung cancer patients remains poor and is strongly related to the stage of disease at the time of diagnosis. Therefore, our study focuses on metastasis formation in LUAD. We performed high-performance liquid chromatography (HPLC) and electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a total of 40 FFPE samples and compared proteomic profiles of primary tumors to those of matched distant metastases. Using differential expression analysis and unsupervised clustering we identified candidate proteins playing a role in metastatic spread. Selected proteins were validated by immunoblotting. Our findings give a better understanding of tumor progression and metastasis formation in LUAD and might help to develop biomarker specific therapy.

2023-11-28 | PXD042604 | Pride

Long non-coding RNA CAR10 promotes lung adenocarcinoma metastasis via miR-203/30/SNAI axis

Project description:Long noncoding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides with limited protein coding potential. Long non-coding RNAs (lncRNAs) play an important role in lung adenocarcinoma (LUAD) metastasis. In this study, we profiled matched tissue from LUAD patients with HTA 2.0 microarray analysis and identified lncRNA- chromatin-associated RNA 10 (CAR10) as obviously clearly overexpressed in LUAD tissues. we demonstrated that CAR10 accelerates tumor growth and promotes metastasis in lung adenocarcinoma. CAR10 was shown to promote epithelial-to-mesenchymal transition (EMT) translation of LUAD cells through sponging miR-30/203, leading to upregulation of SNAI1/2 expression.

2020-10-17 | GSE121397 | GEO

Identification of RAC1 in Promoting Brain Metastasis of Lung Adenocarcinoma using Single-cell Transcriptome Sequencing

Project description:Brain metastases are common in lung adenocarcinoma (LUAD) patients, and by far, the metastasis mechanisms are not fully understood. We performed a comprehensive single-cell level transcriptomic analysis on one LUAD patient with CTC, primary tumor tissue and metastatic tumor tissue using scRNA-seq approach to identify metastasis related biomarkers. Further scRNA-seq were performed on 7 patients to validate the cancer metastatic hallmark. with single cells collected from either metastatic or primary LUAD tissues. we obtained a more comprehensive picture over lung cancer metastasis in the single-cell level, giving a new perspective to the role of RAC1 in the LUAD brain metastasis, and related pathways to participate in the metastasis process.

2022-03-13 | GSE198291 | GEO

Identification and Characterization of a Class of MALAT1-like Genomic Loci

Project description:The MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) gene encodes a non-coding RNA that is processed into a long nuclear retained transcript (MALAT1) and a small cytoplasmic tRNA-like transcript (mascRNA). Using a RNA sequence- and structure-based covariance model, we identified more than 130 genomic loci in vertebrate genomes containing the MALAT1 3’-end triple helix structure and its immediate downstream tRNA-like structure, including 44 in the green lizard Anolis carolinensis. Structural and computational analyses revealed a coevolution of the 3’-end module. MALAT1-like genes in Anolis carolinensis are highly expressed in adult testis, thus we named them testis-abundant long noncoding RNAs (tancRNAs). TancRNA loci produce multiple small RNA species, including piRNAs, from the antisense strand. The coevolved 3’-end of tancRNAs serve as potential targets for the PIWI-piRNA complex. Thus, we have identified an evolutionarily conserved class of lncRNAs with similar structural constraints, post-transcriptional processing, subcellular localization and a distinct function in spermatocytes.

2017-06-08 | GSE97451 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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