Characterization of the Melanoma miRNAome by Deep Sequencing

Background MicroRNAs (miRNAs) are 18–23 nucleotide non-coding RNAs that regulate gene expression in a sequence specific manner. Little is known about the repertoire and function of miRNAs in melanoma or the melanocytic lineage. We therefore undertook a comprehensive analysis of the miRNAome in a diverse range of pigment cells including: melanoblasts, melanocytes, congenital nevocytes, acral, mucosal, cutaneous and uveal melanoma cells. Methodology/Principal Findings We sequenced 12 small RNA libraries using Illumina's Genome Analyzer II platform. This massively parallel sequencing approach of a diverse set of melanoma and pigment cell libraries revealed a total of 539 known mature and mature-star sequences, along with the prediction of 279 novel miRNA candidates, of which 109 were common to 2 or more libraries and 3 were present in all libraries. Conclusions/Significance Some of the novel candidate miRNAs may be specific to the melanocytic lineage and as such could be used as biomarkers to assist in the early detection of distant metastases by measuring the circulating levels in blood. Follow up studies of the functional roles of these pigment cell miRNAs and the identification of the targets should shed further light on the development and progression of melanoma.

[1]  Stefano Volinia,et al.  Altered expression of selected microRNAs in melanoma: antiproliferative and proapoptotic activity of miRNA-155. , 2009, International journal of oncology.

[2]  K. J. Sweeney,et al.  MicroRNAs as Novel Biomarkers for Breast Cancer , 2009, Journal of oncology.

[3]  Michael Rehli,et al.  miRNA expression profiling in melanocytes and melanoma cell lines reveals miRNAs associated with formation and progression of malignant melanoma. , 2009, The Journal of investigative dermatology.

[4]  E. Cuppen,et al.  Limitations and possibilities of small RNA digital gene expression profiling , 2009, Nature Methods.

[5]  Ana M. Aransay,et al.  miRanalyzer: a microRNA detection and analysis tool for next-generation sequencing experiments , 2009, Nucleic Acids Res..

[6]  D. Hu,et al.  MicroRNA-34a inhibits uveal melanoma cell proliferation and migration through downregulation of c-Met. , 2009, Investigative ophthalmology & visual science.

[7]  George A. Calin,et al.  MicroRNAs — the micro steering wheel of tumour metastases , 2009, Nature Reviews Cancer.

[8]  D. Polsky,et al.  Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor , 2009, Proceedings of the National Academy of Sciences.

[9]  A. Srinivasan,et al.  CID-miRNA: a web server for prediction of novel miRNA precursors in human genome. , 2008, Biochemical and biophysical research communications.

[10]  Robert J. Moore,et al.  A microRNA catalog of the developing chicken embryo identified by a deep sequencing approach. , 2008, Genome research.

[11]  Mauro Biffoni,et al.  The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. , 2008, Cancer research.

[12]  R. Place,et al.  MicroRNA-373 induces expression of genes with complementary promoter sequences , 2008, Proceedings of the National Academy of Sciences.

[13]  Lin Zhang,et al.  The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis , 2008, Nature Cell Biology.

[14]  W. Gerald,et al.  Endogenous human microRNAs that suppress breast cancer metastasis , 2008, Nature.

[15]  Tsung-Cheng Chang,et al.  Widespread microRNA repression by Myc contributes to tumorigenesis , 2008, Nature Genetics.

[16]  R. Weinberg,et al.  Tumour invasion and metastasis initiated by microRNA-10b in breast cancer , 2008, Nature.

[17]  J. Steitz,et al.  Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation , 2007, Science.

[18]  Eugene Berezikov,et al.  Mammalian mirtron genes. , 2007, Molecular cell.

[19]  F. Slack,et al.  The let-7 microRNA represses cell proliferation pathways in human cells. , 2007, Cancer research.

[20]  T. Golub,et al.  Impaired microRNA processing enhances cellular transformation and tumorigenesis , 2007, Nature Genetics.

[21]  Anindya Dutta,et al.  The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. , 2007, Genes & development.

[22]  Jason H. Moore,et al.  Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. , 2007, Cancer research.

[23]  C. Croce,et al.  A microRNA expression signature of human solid tumors defines cancer gene targets , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[24]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[25]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[26]  Lin He,et al.  MicroRNAs: small RNAs with a big role in gene regulation , 2004, Nature Reviews Genetics.

[27]  Markus Ringnér,et al.  Microarray expression profiling in melanoma reveals a BRAF mutation signature , 2004, Oncogene.

[28]  D. Fisher,et al.  Transcriptional Regulation of the Melanoma Prognostic Marker Melastatin (TRPM1) by MITF in Melanocytes and Melanoma , 2004, Cancer Research.

[29]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

[30]  M. Herlyn,et al.  Human melanoblasts in culture: expression of BRN2 and synergistic regulation by fibroblast growth factor-2, stem cell factor, and endothelin-3. , 2003, The Journal of investigative dermatology.

[31]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[32]  Wei Chen,et al.  Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: pigmentation marker, ultrastructural and UV-survival studies. , 2003, Pigment cell research.

[33]  P. Pollock,et al.  PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines , 2002, Melanoma research.

[34]  A. Sober,et al.  Melastatin expression and prognosis in cutaneous malignant melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.