This study was aimed to identify novel miRNA biomarkers and explore the cooperative function of multi-RNAs in the progress of primary melanoma. The miRNA expression profile GSE62370 generated from 9 congenital nevi and 92 primary melanoma samples was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between primary melanoma and congenital nevi were compared and the target genes of them were selected. Pathway enrichment analysis and protein/protein interaction (PPI) network of miRNA target genes were performed. In addition, the differential expression of miRNAs to identify the tumor stage-dependent differences in miRNA expression was analyzed. Differentially expressed miRNAs, including 6 upregulated and 23 downregulated, were found in primary melanoma. Besides, the miRNA-associated gene regulatory network revealed 274 nodes, including miR-142-5p and miR-125b, and 307 miRNA-target pairs. miRNA-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, such as melanoma, was found. Target genes in the PPI module were mainly enriched in cancer-related pathways. Finally, the melanoma stage-related overexpressed miR-142-5p and the downregulated miR-550, miR-1826, miR-1201, miR-205, and miR-125b were identified. Some validated miRNAs, including miR-125a/b, let-7a/b, and miR-205, were found and illustrated the reliability of our study. Four novel miRNAs, including miR-142-5p, miR-550a, miR-1826, and miR-1201, were considered to have potential prognostic values for primary melanoma.
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References
1.
AzouryS.C., and LangeJ.R.2014. Epidemiology, risk factors, prevention, and early detection of melanoma. Surg. Clin. North Am. 94, 945–962.
2.
BalchC.M., BuzaidA.C., SoongS.-J., et al.2001. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J. Clin. Oncol. 19, 3635–3648.
3.
BjörnL.O., and McKenzieR.L.2008. Ozone depletion and the effects of ultraviolet radiation, 503–530. In Photo- biology, Björn, L.O., eds. Springer, New York.
4.
BolandG.M., and GershenwaldJ.E.2015. Melanoma survivorship management,2019–239. In Advances in Cancer Survivorship Management. Foxhall, L.E., and Rodriguez, M.A., eds. Springer-Verlag, New York.
5.
CaiH., ChenH., YiT., et al.2013. VennPlex—A novel Venn diagram program for comparing and visualizing datasets with differentially regulated datapoints. PLoS One, 8, e53388.
6.
ChenJ., FeilotterH.E., ParéG.C., et al.2010. MicroRNA-193b represses cell proliferation and regulates cyclin D1 in melanoma. Am. J. Pathol. 176, 2520–2529.
7.
DahlhausM., RoolfC., RuckS., et al.2013. Expression and prognostic significance of hsa-miR-142-3p in acute leukemias. Neoplasma, 60, 432.
8.
DingS., LiangY., ZhaoM., et al.2012. Decreased microRNA-142-3p/5p expression causes CD4+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus. Arthritis Rheum. 64, 2953–2963.
9.
DweepH., StichtC., PandeyP., et al.2011. miRWalk–database: Prediction of possible miRNA binding sites by “walking” the genes of three genomes. J. Biomed. Inform. 44, 839–847.
10.
DynoodtP., SpeeckaertR., De WeverO., et al.2013. miR-145 overexpression suppresses the migration and invasion of metastatic melanoma cells. Int. J. Oncol. 42, 1443–1451.
11.
HannaJ.A., HahnL., AgarwalS., et al.2012. In situ measurement of miR-205 in malignant melanoma tissue supports its role as a tumor suppressor microRNA. Lab. Invest. 92, 1390–1397.
12.
HannifordD., SeguraM.F., ZhongJ., et al.2015a. Identification of metastasis-suppressive microRNAs in primary melanoma. J. Natl. Cancer Inst. 107, dju494.
13.
HannifordD., ZhongJ., KoetzL., et al.2015b. A miRNA-based signature detected in primary melanoma tissue predicts development of brain metastasis. Clin. Cancer Res. 21, 4903–4912.
14.
HirataH., HinodaY., UenoK., et al.2012. MicroRNA-1826 targets VEGFC, beta-catenin (CTNNB1) and MEK1 (MAP2K1) in human bladder cancer. Carcinogenesis, 33, 41–48.
15.
HuY., YiB., HeS., et al.2016. Clinical significance of miR-1826 as a novel prognostic biomarker in colorectal cancer. Anticancer Agents Med. Chem. 16, 1109–1116.
16.
KappelmannM., KuphalS., MeisterG., et al.2013. MicroRNA miR-125b controls melanoma progression by direct regulation of c-Jun protein expression. Oncogene, 32, 2984–2991.
17.
KulkarniR., and BaltimoreD.2013. Elucidating the temporal dynamics of NF-κB activation by TNF-α in melanoma. J. Invest. Dermatol. 133, S227.
18.
LeiZ., XuG., WangL., et al.2014. MiR-142-3p represses TGF-β-induced growth inhibition through repression of TGFβR1 in non-small cell lung cancer. FASEB J. 28, 2696–2704.
19.
LiuS., KumarS.M., LuH., et al.2012. MicroRNA-9 up-regulates E-cadherin through inhibition of NF-κB1-Snail1 pathway in melanoma. J. Pathol. 226, 61–72.
20.
Lopez-GuerreroJ.A., Fernandez-SerraA., CalabuigS., et al.2014. Disregulation of mir-550 and let-7e in intestinal high-risk localized GIST: A GEIS study. Journal of Clinical Oncology. 32, 10514.
21.
MairingerF.D., TingS., WernerR., et al.2014. Different micro-RNA expression profiles distinguish subtypes of neuroendocrine tumors of the lung: Results of a profiling study. Mod. Pathol. 27, 1632–1640.
22.
MartiniukF., DamianD. L., ThompsonJ. F., et al.2010. TH17 is involved in the remarkable regression of metastatic malignant melanoma to topical diphencyprone. J. Drugs Dermatol. 9, 1368–1372.
23.
MüllerD., and BosserhoffA.2008. Integrin β3 expression is regulated by let-7a miRNA in malignant melanoma. Oncogene, 27, 6698–6706.
24.
MuellerD.W., RehliM., and BosserhoffA.K.2009. miRNA expression profiling in melanocytes and melanoma cell lines reveals miRNAs associated with formation and progression of malignant melanoma. J. Invest. Dermatol. 129, 1740–1751.
25.
O'LearyD.P., ByrnesK.G., PowerD.G., et al.2015. Surgical management of metastatic melanoma in the era of targeted systemic therapies. Melanoma Res. 25, 1–8.
26.
PenchevaN., TranH., BussC., et al.2012. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell, 151, 1068–1082.
27.
PhilippidouD., SchmittM., MoserD., et al.2010. Signatures of microRNAs and selected microRNA target genes in human melanoma. Cancer Res. 70, 4163–4173.
28.
SandM., SkryganM., SandD., et al.2013. Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi. Cell Tissue Res. 351, 85–98.
29.
SchultzJ., LorenzP., GrossG., et al.2008. MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell Res. 18, 549–557.
30.
ShannonP., MarkielA., OzierO., et al.2003. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504.
31.
SmythG.K.2005. Limma: Linear models for microarray data, 397–420. In Bioinformatics and Computational Biology Solutions Using R and Bioconductor, Gentleman, R., Carey, V.J., Huber, W., Irizarry, R.A., and Dudoit, S., eds. Springer, New York.
32.
SzklarczykD., FranceschiniA., WyderS., et al.2014. STRING v10: Protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43, D447–D452.
33.
TianQ., LiangL., DingJ., et al.2012. MicroRNA-550a acts as a pro-metastatic gene and directly targets cytoplasmic polyadenylation element-binding protein 4 in hepatocellular carcinoma. PLoS One, 7, e48958.
34.
WigunaA.P.2014. Immunoregulation in Melanoma: Role of IL-10 and TGF-beta. Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Berlin.
35.
XiaoF., ZuoZ., CaiG., et al.2009. miRecords: An integrated resource for microRNA–target interactions. Nucleic Acids Res. 37, D105–D110.
36.
YuG., WangL. G., HanY., et al.2012. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS, 16, 284–287.
37.
ZhengZ., DingM., NiJ., et al.2015. miR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1. Oncol. Rep. 33, 1291–1299.
