Evaluation of melanoma cells kinome and microRNAs expression reprogramming in response to microRNA 34a mimic

Abstract

Acquisition of resistance, aggressiveness and immune evasion are limiting factors to the effectiveness of melanoma therapy. Thus, identifying a new candidate with therapeutic potential, as well as the definition of its molecular mechanism of action may contribute to the development of more efficient therapy protocols that could provide a better quality of life for the patients. We have recently observed that human melanoma cells transfected with the mimic of miR-34a showed a decrease in the proliferation rate, which was followed by an increased expression of proteins associated with cell death. Once protein kinases are normally constitutively active in tumor cells our hypothesis is that the effect of miR-34a on melanoma cells could be related to the modulation of kinases. Accordingly, the main objective of this proposal is to define the kinome profile in the melanoma cells transfected with miR-34a mimic. Our research group has used the Pepchip technique to study the global modulation of kinases in cellular processes such as osteogenesis, cell differentiation and tumor resistance. On the other hand, this approach allows us not only to elucidate the molecular mechanism of some biological effect, but also to predict potential side effects of a drug candidate. Therefore, this proposal could generate new information about the biology of melanoma, as well as provide the molecular basis of the miR-34a role as a tumor suppressor.