Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Nov 7;18(11):2354.
doi: 10.3390/ijms18112354.

miRNAs, Melanoma and Microenvironment: An Intricate Network

Gabriele Romano  1 , Lawrence N Kwong  2
Affiliations
Review

miRNAs, Melanoma and Microenvironment: An Intricate Network

Gabriele Romano et al. Int J Mol Sci. .

Abstract

miRNAs are central players in cancer biology and they play a pivotal role in mediating the network communication between tumor cells and their microenvironment. In melanoma, miRNAs can impair or facilitate a wide array of processes, and here we will focus on: the epithelial to mesenchymal transition (EMT), the immune milieu, and metabolism. Multiple miRNAs can affect the EMT process, even at a distance, for example through exosome-mediated mechanisms. miRNAs also strongly act on some components of the immune system, regulating the activity of key elements such as antigen presenting cells, and can facilitate an immune evasive/suppressive phenotype. miRNAs are also involved in the regulation of metabolic processes, specifically in response to hypoxic stimuli where they can mediate the metabolic switch from an oxidative to a glycolytic metabolism. Overall, this review discusses and summarizes recent findings on miRNA regulation in the melanoma tumor microenvironment, analyzing their potential diagnostic and therapeutic applications.

Keywords: epithelial to mesenchymal transition (EMT); hypoxia; immune system; melanoma; metabolism; miRNA; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MicroRNA (miRNA)-mediated regulation of epithelial to mesenchymal transition (EMT) in melanoma. miRNAs can facilitate or impair EMT through transcriptional, post-transcriptional or epigenetic mechanisms in a context dependent manner. Red T symbols indicate repression, green arrows indicate up-regulation.
Figure 2
Figure 2
Innate and adaptive immune regulation by miRNAs. miRNAs are involved both in soluble factor and receptor regulation of immune cells, frequently exerting an immune suppressive/evading phenotype. CTL: Cytotoxic T Lymphocyte; FoxP3+: Regulatory T cells; M2 Mϕ: M2 Macrophage; MDSC: myeloid-derived suppressor cell. Red T symbols indicate repression, green arrows indicate up-regulation.
Figure 3
Figure 3
miRNA participate in melanoma metabolic regulation. Hypoxia can favor a tumor metabolic switch from an oxidative metabolism (OxPhos) to a glycolytic one. miRNA are involved in tumor cell response to hypoxia and neo-angiogenesis. Red T symbols indicate repression, green arrows indicate up-regulation.
See this image and copyright information in PMC

References

    1. Larkin J., Chiarion-Sileni V., Gonzalez R., Grob J.J., Cowey C.L., Lao C.D., Schadendorf D., Dummer R., Smylie M., Rutkowski P., et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 2015;373:23–34. doi: 10.1056/NEJMoa1504030. - DOI - PMC - PubMed
    1. Postow M.A., Chesney J., Pavlick A.C., Robert C., Grossmann K., McDermott D., Linette G.P., Meyer N., Giguere J.K., Agarwala S.S., et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 2015;372:2006–2017. doi: 10.1056/NEJMoa1414428. - DOI - PMC - PubMed
    1. Konieczkowski D.J., Johannessen C.M., Abudayyeh O., Kim J.W., Cooper Z.A., Piris A., Frederick D.T., Barzily-Rokni M., Straussman R., Haq R., et al. A melanoma cell state distinction influences sensitivity to mapk pathway inhibitors. Cancer Discov. 2014;4 doi: 10.1158/2159-8290.CD-13-0424. - DOI - PMC - PubMed
    1. Richard G., Dalle S., Monet M.A., Ligier M., Boespflug A., Pommier R.M., de la Fouchardière A., Perier-Muzet M., Depaepe L., Barnault R., et al. ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors. EMBO Mol. Med. 2016;8:1143–1161. doi: 10.15252/emmm.201505971. - DOI - PMC - PubMed
    1. Caramel J., Papadogeorgakis E., Hill L., Browne G.J., Richard G., Wierinckx A., Saldanha G., Osborne J., Hutchinson P., Tse G., et al. A switch in the expression of embryonic emt-inducers drives the development of malignant melanoma. Cancer Cell. 2013;24:466–480. doi: 10.1016/j.ccr.2013.08.018. - DOI - PubMed

LinkOut - more resources