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Comparative transcriptome profiling of genes and pathways related to acquired and intrinsic resistance to BRAF inhibitor
Author(s) -
Lee Michael,
Hwang SungHee
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.474.7
Subject(s) - biology , transcriptome , kegg , cancer research , gene expression profiling , computational biology , microbiology and biotechnology , gene , genetics , gene expression
Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA‐Seq analysis with BRAF inhibitor‐sensitive (A375P) and ‐resistant (A375P/Mdr with acquired resistance and SK‐MEL‐2 with intrinsic resistance) melanoma cell lines, to reveal the genes and pathways potentially involved in intrinsic and acquired resistance to BRAF inhibitors. A total of 546 differentially expressed genes (DEGs), including 239 up‐regulated and 307 down‐regulated genes, were identified in both intrinsic and acquired resistant cells. Gene ontology (GO) analysis revealed that the top 10 biological processes associated with these genes included angiogenesis, immune response, cell adhesion, antigen processing and presentation, extracellular matrix organization, osteoblast differentiation, collagen catabolic process, viral entry into host cell, cell migration, and positive regulation of protein kinase B signaling. In addition, using the PANTHER GO classification system, we showed that the highest enriched GOs targeted by the 546 DEGs were responses to cellular processes (ontology: biological process), binding (ontology: molecular function), and cell subcellular localization (ontology: cellular component). Ingenuity pathway analysis (IPA) network analysis showed a network that was common to two BRAF inhibitor‐resistant cells. Taken together, the present study may provide a useful platform to further reveal biological processes associated with BRAF inhibitor resistance, and present areas for therapeutic tool development to overcome BRAF inhibitor resistance. Support or Funding Information Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2016R1D1A1B03930193) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .