MicroRNAs in melanoma development and resistance to target therapy
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Luigi Fattore1, Susan Costantini2, Debora Malpicci3, Ciro Francesco Ruggiero3, Paolo Antonio Ascierto1, Carlo M. Croce4, Rita Mancini5 and Gennaro Ciliberto1,6
1 Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione G. Pascale”, Naples, Italy
2 CROM, Istituto Nazionale Tumori “Fondazione G. Pascale”-IRCCS, Naples, Italy
3 Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Catanzaro “Magna Graecia”, Catanzaro, Italy
4 Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
5 Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy
6 IRCCS Istituto Nazionale Tumori “Regina Elena”, Rome, Italy
Gennaro Ciliberto, email:
Keywords: melanoma, miRNA, target therapy, drug resistance, intracellular pathways
Received: August 04, 2016 Accepted: January 10, 2017 Published: January 19, 2017
microRNAs constitute a complex class of pleiotropic post-transcriptional regulators of gene expression involved in the control of several physiologic and pathologic processes. Their mechanism of action is primarily based on the imperfect matching of a seed region located at the 5’ end of a 21-23 nt sequence with a partially complementary sequence located in the 3’ untranslated region of target mRNAs. This leads to inhibition of mRNA translation and eventually to its degradation. Individual miRNAs are capable of binding to several mRNAs and several miRNAs are capable of influencing the function of the same mRNAs. In recent years networks of miRNAs are emerging as capable of controlling key signaling pathways responsible for the growth and propagation of cancer cells. Furthermore several examples have been provided which highlight the involvement of miRNAs in the development of resistance to targeted drug therapies. In this review we provide an updated overview of the role of miRNAs in the development of melanoma and the identification of the main downstream pathways controlled by these miRNAs. Furthermore we discuss a group of miRNAs capable to influence through their respective up- or down-modulation the development of resistance to BRAF and MEK inhibitors.
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