Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Differential Gene Expression Common to Acquired and Intrinsic Resistance to BRAF Inhibitor Revealed by RNA-Seq Analysis

  • Ahn, Jun-Ho (System Toxicology Research Center, Korea Institute of Toxicology) ;
  • Hwang, Sung-Hee (Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University) ;
  • Cho, Hyun-Soo (Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Michael (Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University)
  • Received : 2018.07.17
  • Accepted : 2018.08.16
  • Published : 2019.05.01
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Abstract

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 PAN-THER 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 inhibitorresistant 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.

Keywords

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