Fattore Luigi, Costantini Susan, Malpicci Debora, Ruggiero Ciro Francesco, Ascierto Paolo Antonio, Croce Carlo M, Mancini Rita, Ciliberto Gennaro
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale", Napoli, Italia.
CROM, Istituto Nazionale Tumori "Fondazione G. Pascale"-IRCCS, Napoli, Italia.
Oncotarget. 2017 Mar 28;8(13):22262-22278. doi: 10.18632/oncotarget.14763.
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.
微小RNA构成了一类复杂的多效性转录后基因表达调节因子，参与多种生理和病理过程的调控。它们的作用机制主要基于位于21 - 23个核苷酸序列5'端的种子区域与靶mRNA 3'非翻译区中部分互补序列的不完全匹配。这导致mRNA翻译受到抑制并最终降解。单个微小RNA能够结合多个mRNA，多个微小RNA也能够影响相同mRNA的功能。近年来，微小RNA网络逐渐显现出能够控制负责癌细胞生长和增殖的关键信号通路。此外，已有多个例子表明微小RNA参与了对靶向药物治疗耐药性的形成。在本综述中，我们提供了微小RNA在黑色素瘤发生发展中的作用以及这些微小RNA所控制的主要下游通路的最新概述。此外，我们还讨论了一组能够通过上调或下调其表达来影响对BRAF和MEK抑制剂耐药性形成的微小RNA。
