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Establishment and characterization of NF2/CDKN2A-double knockout gene in human mesothelial cell line generated by using CRISPR/Cas9 technology

ABSTRACT: Establishment and characterization of NF2/CDKN2A-double knockout gene in human mesothelial cell line generated by using CRISPR/Cas9 technology

PROVIDER: PRJNA560052 | ENA |

REPOSITORIES: ENA

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Establishment and characterization of NF2/CDKN2A-double knockout gene in human mesothelial cell line generated by using CRISPR/Cas9 technology

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Inactivation of Bap1 Cooperates with Losses of Nf2 and Cdkn2a to Drive the Development of Pleural Malignant Mesothelioma in Conditional Mouse Models

Project description:Mutations/deletions of BAP1, CDKN2A, and NF2 are the most frequent genetic lesions in human MM. We introduced various combinations of these deletions in the pleura of conditional knockout (CKO) mice, focusing on the contribution of Bap1 loss.

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Establishment and characterization of CRISPR/Cas9-mediated Merlin/NF2 knockout human mesothelial cell line Met-5A

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Establishment and characterization of BAP1 knockout gene in human mesothelial cell line generated by using CRISPR/Cas9 technology

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Inactivation of p21-Activated Kinase 2 (Pak2) Inhibits the Development of Nf2-Deficient Tumors by Restricting Downstream Hedgehog and Wnt Signaling

Project description:Since loss of the NF2 tumor suppressor gene results in p21-activated kinase (Pak) activation, PAK inhibitors hold promise for the treatment of NF2-deficient tumors. To test this possibility, we asked if loss of Pak2, a highly expressed group I PAK member, affects the development of malignant mesothelioma in Nf2;Cdkn2a-deficient (NC) mice and the growth properties of NC mesothelioma cells in culture. In vivo, deletion of Pak2 resulted in a markedly decreased incidence and delayed onset of both pleural and peritoneal malignant mesotheliomas in NC mice. In vitro, Pak2 deletion decreased malignant mesothelioma cell viability, migration, clonogenicity, and spheroid formation. RNA-seq analysis demonstrated downregulated expression of Hedgehog and Wnt pathway genes in NC;Pak2-/- mesothelioma cells versus NC;Pak2+/+ mesothelioma cells. Targeting of the Hedgehog signaling component Gli1 or its target gene Myc inhibited cell viability and spheroid formation in NC;P+/+ mesothelioma cells. Kinome profiling uncovered kinase changes indicative of EMT in NC;Pak2-/- mesothelioma cells, suggesting that Pak2-deficient malignant mesotheliomas can adapt by reprogramming their kinome in the absence of Pak activity. The identification of such compensatory pathways offers opportunities for rational combination therapies to circumvent resistance to anti-PAK drugs.

2023-03-10 | PXD030571 | Pride

Whole transcriptome analysis of rat peritoneal cells in a TGFβ1 induced mesothelial-to-mesenchymal transition

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2021-12-03 | GSE168340 | GEO

Identification of mesothelial-to-mesenchymal gene signature in ascitic fluid-isolated mesothelial cells through RNA-sequencing

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