Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment
- PMID: 38875320
- DOI: 10.1126/sciimmunol.adh5462
Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment
Abstract
Expression of the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) correlates with tumor progression and metastasis in many tumor types. However, the impact and mechanism of action by which MALAT1 promotes metastatic disease remain elusive. Here, we used CRISPR activation (CRISPRa) to overexpress MALAT1/Malat1 in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. Malat1 overexpression was sufficient to promote the progression of LUAD to metastatic disease in mice. Overexpression of MALAT1/Malat1 enhanced cell mobility and promoted the recruitment of protumorigenic macrophages to the tumor microenvironment through paracrine secretion of CCL2/Ccl2. Ccl2 up-regulation was the result of increased global chromatin accessibility upon Malat1 overexpression. 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.
Update of
-
Overexpressed Malat1 Drives Metastasis through Inflammatory Reprogramming of Lung Adenocarcinoma Microenvironment.bioRxiv [Preprint]. 2023 Mar 23:2023.03.20.533534. doi: 10.1101/2023.03.20.533534. bioRxiv. 2023. Update in: Sci Immunol. 2024 Jun 14;9(96):eadh5462. doi: 10.1126/sciimmunol.adh5462. PMID: 36993368 Free PMC article. Updated. Preprint.
Similar articles
-
Overexpressed Malat1 Drives Metastasis through Inflammatory Reprogramming of Lung Adenocarcinoma Microenvironment.bioRxiv [Preprint]. 2023 Mar 23:2023.03.20.533534. doi: 10.1101/2023.03.20.533534. bioRxiv. 2023. Update in: Sci Immunol. 2024 Jun 14;9(96):eadh5462. doi: 10.1126/sciimmunol.adh5462. PMID: 36993368 Free PMC article. Updated. Preprint.
-
LncRNA MALAT1 Facilitates Ovarian Cancer Progression through Promoting Chemoresistance and Invasiveness in the Tumor Microenvironment.Int J Mol Sci. 2021 Sep 22;22(19):10201. doi: 10.3390/ijms221910201. Int J Mol Sci. 2021. PMID: 34638541 Free PMC article.
-
In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma.Cancer Discov. 2020 Feb;10(2):270-287. doi: 10.1158/2159-8290.CD-19-0780. Epub 2019 Nov 19. Cancer Discov. 2020. PMID: 31744829 Free PMC article.
-
HCP5 is a SMAD3-responsive long non-coding RNA that promotes lung adenocarcinoma metastasis via miR-203/SNAI axis.Theranostics. 2019 Apr 13;9(9):2460-2474. doi: 10.7150/thno.31097. eCollection 2019. Theranostics. 2019. PMID: 31131047 Free PMC article.
-
Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 promotes lung adenocarcinoma by directly interacting with specificity protein 1.Cancer Sci. 2018 May;109(5):1346-1356. doi: 10.1111/cas.13587. Epub 2018 Apr 22. Cancer Sci. 2018. PMID: 29575609 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous
