dbDEMC: a database of differentially expressed miRNAs in human cancers

BackgroundMicroRNAs (miRNAs) are small noncoding RNAs about 22 nt long that negatively regulate gene expression at the post-transcriptional level. Their key effects on various biological processes, e.g., embryonic development, cell division, differentiation and apoptosis, are widely recognized. Evidence suggests that aberrant expression of miRNAs may contribute to many types of human diseases, including cancer. Here we present a database of differentially expressed miRNAs in human cancers (dbDEMC), to explore aberrantly expressed miRNAs among different cancers.ResultsWe collected the miRNA expression profiles of 14 cancer types, curated from 48 microarray data sets in peer-reviewed publications. The Significance Analysis of Microarrays method was used to retrieve the miRNAs that have dramatically different expression levels in cancers when compared to normal tissues. This database provides statistical results for differentially expressed miRNAs in each data set. A total of 607 differentially expressed miRNAs (590 mature miRNAs and 17 precursor miRNAs) were obtained in the current version of dbDEMC. Furthermore, low-throughput data from the same literature were also included in the database for validation. An easy-to-use web interface was designed for users. Annotations about each miRNA can be queried through miRNA ID or miRBase accession numbers, or can be browsed by different cancer types.ConclusionsThis database is expected to be a valuable source for identification of cancer-related miRNAs, thereby helping with the improvement of classification, diagnosis and treatment of human cancers. All the information is freely available through http://159.226.118.44/dbDEMC/index.html.

[1]  Gapped BLAST and PSI-BLAST: A new , 1997 .

[2]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[5]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[6]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[7]  P. Brown,et al.  Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Danchin,et al.  Bmc Genomics , 2004 .

[9]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[10]  Anton J. Enright,et al.  Human MicroRNA Targets , 2004, PLoS biology.

[11]  K. Lindblad-Toh,et al.  Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals , 2005, Nature.

[12]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[13]  E. Miska,et al.  MicroRNA functions in animal development and human disease , 2005, Development.

[14]  Y. Yatabe,et al.  A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. , 2005, Cancer research.

[15]  M. Byrom,et al.  Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis , 2005, Nucleic acids research.

[16]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[17]  H. Horvitz,et al.  MicroRNA Expression in Zebrafish Embryonic Development , 2005, Science.

[18]  Kathryn A. O’Donnell,et al.  c-Myc-regulated microRNAs modulate E2F1 expression , 2005, Nature.

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

[20]  R. Shiekhattar,et al.  MicroRNA biogenesis and cancer. , 2005, Cancer research.

[21]  Emmanuel Barillot,et al.  ITTACA: a new database for integrated tumor transcriptome array and clinical data analysis , 2005, Nucleic Acids Res..

[22]  Yu Zhang,et al.  HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma , 2005, Nucleic Acids Res..

[23]  Xijin Ge,et al.  SAGE detects microRNA precursors , 2006, BMC Genomics.

[24]  K. Ghoshal,et al.  Downregulation of miR‐122 in the rodent and human hepatocellular carcinomas , 2006, Journal of cellular biochemistry.

[25]  Yukio Kitade,et al.  Downregulation of microRNAs‐143 and ‐145 in B‐cell malignancies , 2007, Cancer science.

[26]  E. Miska,et al.  MicroRNA—implications for cancer , 2007, Virchows Archiv.

[27]  R. Vyzula,et al.  Altered Expression of miR-21, miR-31, miR-143 and miR-145 Is Related to Clinicopathologic Features of Colorectal Cancer , 2008, Oncology.

[28]  J. Cheng,et al.  Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis , 2008, Child's Nervous System.

[29]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

[30]  Yi Zhao,et al.  The Properties and Functions of Virus Encoded microRNA, siRNA, and Other Small Noncoding RNAs , 2008, Critical reviews in microbiology.

[31]  Doron Betel,et al.  The microRNA.org resource: targets and expression , 2007, Nucleic Acids Res..

[32]  Yu Liang,et al.  A quantitative PCR method to detect blood microRNAs associated with tumorigenesis in transgenic mice , 2008, Molecular Cancer.

[33]  Sanghyuk Lee,et al.  miRGator: an integrated system for functional annotation of microRNAs , 2007, Nucleic Acids Res..

[34]  Yiwei Li,et al.  MicroRNA and Cancer: Tiny Molecules with Major Implications , 2008, Current genomics.

[35]  Liu Hong,et al.  miR‐15b and miR‐16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells , 2008, International journal of cancer.

[36]  Domenico Coppola,et al.  MicroRNA-221/222 Negatively Regulates Estrogen Receptorα and Is Associated with Tamoxifen Resistance in Breast Cancer* , 2008, Journal of Biological Chemistry.

[37]  B. White,et al.  Coordinate Regulation of FOXO1 by miR-27a, miR-96, and miR-182 in Breast Cancer Cells , 2009, The Journal of Biological Chemistry.

[38]  P. Galle,et al.  High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. , 2009, World journal of gastroenterology.

[39]  S. Sherman,et al.  Germline mutation of microRNA-125a is associated with breast cancer , 2009, Journal of Medical Genetics.

[40]  S. Swisher,et al.  Tumorigenesis and Neoplastic Progression MicroRNA-196 a Is a Potential Marker of Progression during Barrett ’ s Metaplasia-Dysplasia-Invasive Adenocarcinoma Sequence in Esophagus , 2010 .

[41]  Yadong Wang,et al.  miR2Disease: a manually curated database for microRNA deregulation in human disease , 2008, Nucleic Acids Res..

[42]  Dennis B. Troup,et al.  NCBI GEO: archive for high-throughput functional genomic data , 2008, Nucleic Acids Res..

[43]  Liang Xu,et al.  MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications , 2009, The AAPS Journal.

[44]  Chuan Wang,et al.  dbDEPC: a database of Differentially Expressed Proteins in human Cancers , 2009, Nucleic Acids Res..

[45]  V. Thayanithy,et al.  S-MED: Sarcoma microRNA Expression Database , 2010, Laboratory Investigation.

[46]  C. Cole,et al.  COSMIC: the catalogue of somatic mutations in cancer , 2011, Genome Biology.