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Overexpressed Malat1 drives metastasis through inflammatory reprogramming of lung adenocarcinoma microenvironment

GSE266561 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/05/08 Platform GPL24247
Summary
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.
Published in
Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment
Martinez-Terroba E, Plasek-Hegde LM, Chiotakakos I et al. · Science immunology 2024 · PMID 38875320 · doi:10.1126/sciimmunol.adh5462
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Also filed as BioProject PRJNA1107590 and SRA study SRP505684. Searching any of these in the dataset finder brings you back here.

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