الفهرس 
Title : Role of Exosomes in the Development of Drug Resistance in Cancer
ContantsOnly 14 pages are availabe for public view
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Abstract
Melanoma expressing BRAFV600E mutation causes 60{u2013}80% of skin cancer- related deaths. Vemurafenib is an effective gene-targeted therapy for BRAFV600E- associated melanomas. Despite the progression-free survival correlated with BRAF inhibition by vemurafenib, resistance often emerges immediately after its antitumor effect. Tumor microenvironment has been widely accepted to participate in drug resistance in cancer. Among the extracellular vesicles, exosomes have been identified as nanovesicles (30-120 nm) that secreted to facilitate the intercellular crosstalk. Exosomes shuttle various bioactive molecules, such as proteins, DNA and microRNAs (miRNAs), from a donor cell to induce genetic modifications in a recipient cell. MicroRNAs are non-coding RNA molecules that function as gene regulators at post-transcriptional level. Exosomal miRNAs have been reported to control the expression of various genes that are involved in oncogenic signal transduction in cancer, with a subsequent alterations in cell growth, cell cycle control and apoptosis programs. Accordingly, this study aimed to investigate the role of exosomal miRNAs in promoting vemurafenib resistance in BRAFV600E-associated melanoma. In this study, vemurafenib-sensitive (parental) (A375 and WM983B) and their respective resistant (A375-NRASQ61K and WM983B-BR) melanoma cells were used; all of which harbor mutant BRAFV600E. Microarray analysis followed by qPCR were performed to identify the differentially expressed exosomal miRNAs in resistant versus parental melanoma cells. Then, transfection with miRNA mimics and inhibitors was used to investigate their functional significance; and western blot analysis was performed to identify the expression of miRNAs target genes, which was then verified in human melanoma samples