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| Status |
Public on May 08, 2024 |
| Title |
Overexpressed Malat1 drives metastasis through inflammatory reprogramming of lung adenocarcinoma microenvironment |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| 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.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for isolated tumor cells with or without targeted Malat1 overexpression in KP mouse model of lung adenocarcinoma.
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| Contributor(s) |
Zamudio JR, Dimitrova N |
| Citation(s) |
38875320 |
| |
| Submission date |
May 03, 2024 |
| Last update date |
Aug 07, 2024 |
| Contact name |
Jesse R Zamudio |
| E-mail(s) |
[email protected]
|
| Organization name |
University of California, Los Angeles
|
| Department |
MCDB
|
| Lab |
Zamudio
|
| Street address |
610 CHARLES E. YOUNG DRIVE EAST BOX 957239
|
| City |
LOS ANGELES |
| State/province |
CA |
| ZIP/Postal code |
90095-7239 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1107590 |
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