Effect Of Restoration Of Microrna-18a On Improvement Of Imatinib Therapy On Secondary Imatinib-Resistance Metastatic Melanoma.

9040 Background: Imatinib generated remarkable clinical response in melanomas harboring c-kit mutation. However, melanoma resistance to imatinib develops rather quickly in most of the patients. It has been shown that gene mutations, translocations, deletions, amplifications, and epigenetic changes are involved in the process of secondary imatinib-resistance in GI stromal tumor. But imatinib resistance in melanoma has not been well evaluated. Methods: The level of miRNAs expression was initially discovered through miRNA profiling using pretreatment and post treatment imatinib resistant melanoma tissues, and then confirmed by quantitative PCR. Scratch wound and in vitro invasion assays were performed to evaluate cell migration and invasion. Luciferase reporter assays, immunoblots, and immunohistochemistry analyses were conducted to examine the association between miR-18a and their targets in imatinib-resistant cell and specimens. Results: miR-18a was dramatically down-regulated in secondary imatinib-resista...