Abstract
The number of treatment options for melanoma patients has grown in the past few years, leading to considerable improvements in both overall and progression-free survival. Targeted therapies and immune checkpoint inhibitors have opened a new era in the management of melanoma patients. Despite the clinical advances, further research efforts are needed to identify other “druggable” targets and new biomarkers to improve the stratification of melanoma patients who could really benefit from targeted and immunotherapies. To this end, many studies have focused on the role of microRNAs (miRNAs) that are small non-coding RNAs (18-25 nucleotides in length), which post-transcriptionally regulate the expression of their targets. In cancer, they can behave either as oncogenes or oncosuppressive genes and play a central role in many intracellular pathways involved in proliferation and invasion. Given their modulating activity on the transcriptional landscape, their biological role is under investigation to study resistance mechanisms. They are able to mediate the communication between tumor cells and their microenvironment and regulate tumor immunity through direct regulation of the genes involved in immune activation or suppression. To date, a very promising miRNA-based strategy is to use them as prognosis and diagnosis biomarkers both as cell-free miRNAs and extracellular-vesicle miRNAs. However, miRNAs have a complex role since they target different genes in different cellular conditions. Thus, the ultimate aim of studies has been to recapitulate their role in melanoma in biological networks that account for miRNA/gene expression and mutational state. In this review, we will provide an overview of current scientific knowledge regarding the oncogenic or oncosuppressive role of miRNAs in melanoma and their use as biomarkers, with respect to approved therapies for melanoma treatment.
Highlights
IntroductionCutaneous melanoma is one of the most aggressive types of cancer worldwide, with an incidence that has been increasing over the past 50 years [1]
Cutaneous melanoma is one of the most aggressive types of cancer worldwide, with an incidence that has been increasing over the past 50 years [1].It occurs from the malignant transformation of melanocytes induced mainly by exposure to intense and prolonged ultraviolet radiation
Cells treated with Vemurafenib [32]. Both neurofibromin 1 (NF1) direct silencing with siRNA and miR-514a upregulation lead to decreased NF1 levels and considerably reduce drug sensitivity in the short term in vitro cell proliferation assays [32]
Summary
Cutaneous melanoma is one of the most aggressive types of cancer worldwide, with an incidence that has been increasing over the past 50 years [1] It occurs from the malignant transformation of melanocytes induced mainly by exposure to intense and prolonged ultraviolet radiation. Targeted molecular therapies against specific mutations [2,3] and systemic immunotherapies including immune checkpoint inhibitors [4,5,6], have recently emerged, replacing conventional chemotherapy [7].Notwithstanding the success of the new therapeutic approaches, many research groups have been working to enhance our knowledge of melanoma biology and to identify further reliable biomarkers. 8), called the “seed region,” and play a role as oncogenes or oncosuppressors [8] They regulate gene expression at the post-transcriptional and translational levels through degradation of mRNA or a translation block. This review discusses the state of the art of studies on miRNAs and their role in response to therapies, their relationship with other “druggable” pathways, and their potential use as clinical biomarkers
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