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Identification of the role of tumor intrinsic Malat1 in regulation of immune microenvironment [scRNA-seq]

ABSTRACT: Identification of the role of tumor intrinsic Malat1 in regulation of immune microenvironment [scRNA-seq]

PROVIDER: PRJNA762374 | ENA |

REPOSITORIES: ENA

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Identification of the role of tumor intrinsic Malat1 in regulation of immune microenvironment [scRNA-seq]

Project description:We have injected 4T1-TGL breast cancer cells into Balbc mice through tail vein. In order to see immune cells infiltration, we have isolated CD45+ cells from these mice lungs at different time points by FACS. These isolated cells were further subjected for scRNA-seq. For base line we have isolated CD45+ cells from Naive balbc mice.

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Overexpressed Malat1 drives metastasis through inflammatory reprogramming of lung adenocarcinoma microenvironment

Project description: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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Overexpressed Malat1 drives metastasis through inflammatory reprogramming of lung adenocarcinoma microenvironment

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Differential Gene expression in the mouse mammary tumors of PyMT-Malat1 wild-type (WT), PyMT-Malat1 knockout (KO) and PyMT-Malat1 knockout with Malat1 transgene expression (TG)

Project description:Previously, lncRNA Malat1 knockout mice were generated by insertional inactivation. By crossing this line to MMTV-PyMT mammary tumor mouse model, we produced PyMT;Malat1 wild-type (WT) and PyMT;Malat1 knockout (KO). Furthermore, we generated Malat1 transgenic mice by targeting ROSA26 locus and bred them to PyMT;Malat1 knockout mice to produce Malat1-rescued PyMT;Malat1 knockout;Malat1 transgenic animals (TG). Using mammary tumors from the three groups of animals, we performed RNA-Seq analysis to identify differentially up-regulated genes in KO tumors to find novel target genes of YAP-TEAD pathway.

2018-09-18 | GSE110239 | GEO

Identification of Malat1-chromatin interaction by ChIRP-seq

Project description:We performed Malat1 pulldown using biotin labeled Stellaris Oligo in 4T1-TGL WT cells.

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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

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