RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment
Autor: | Čermák, Vladimír, Škarková, Aneta, Merta, Ladislav, Kolomazníková, Veronika, Palušová, Veronika, Uldrijan, Stjepan, Rösel, Daniel, Brábek, Jan |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Pyridines
lcsh:QR1-502 Naphthalenes p38 Mitogen-Activated Protein Kinases lcsh:Microbiology Cell Line Tumor Tumor Microenvironment melanoma Humans cancer metastasis RNA-Seq Protein Kinase Inhibitors Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction Communication Gene Expression Profiling amoeboid invasion Imidazoles Cell Differentiation Gene Expression Regulation Neoplastic Gene Ontology Phenotype phenotype switch Pyrazoles Collagen |
Zdroj: | Biomolecules, Vol 11, Iss 449, p 449 (2021) Biomolecules |
Popis: | Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid-mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis. |
Databáze: | OpenAIRE |
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