03230nas a2200709 4500008004100000022001400041245010600055210006900161260001600230300001100246490000800257520120600265653001801471653002001489653002401509653002101533653001101554653003001565653004301595653001801638653001101656653001401667653002101681653002201702653002101724653001901745653002201764100001501786700002101801700001801822700002601840700001901866700001401885700002001899700002501919700002301944700002001967700002601987700002102013700001702034700001802051700001502069700001602084700001602100700002402116700001802140700002402158700002902182700002002211700002502231700002402256700002202280700001802302700001802320700002002338700002202358700002302380700003002403700002002433700001902453856004802472 2008 eng d a1091-649000aGenomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.0 aGenomic and epigenetic alterations deregulate microRNA expressio c2008 May 13 a7004-90 v1053 a
MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as negative gene regulators. miRNA deregulation is involved in the initiation and progression of human cancer; however, the underlying mechanism and its contributions to genome-wide transcriptional changes in cancer are still largely unknown. We studied miRNA deregulation in human epithelial ovarian cancer by integrative genomic approach, including miRNA microarray (n = 106), array-based comparative genomic hybridization (n = 109), cDNA microarray (n = 76), and tissue array (n = 504). miRNA expression is markedly down-regulated in malignant transformation and tumor progression. Genomic copy number loss and epigenetic silencing, respectively, may account for the down-regulation of approximately 15% and at least approximately 36% of miRNAs in advanced ovarian tumors and miRNA down-regulation contributes to a genome-wide transcriptional deregulation. Last, eight miRNAs located in the chromosome 14 miRNA cluster (Dlk1-Gtl2 domain) were identified as potential tumor suppressor genes. Therefore, our results suggest that miRNAs may offer new biomarkers and therapeutic targets in epithelial ovarian cancer.
10aDNA, Neoplasm10aDown-Regulation10aEpigenesis, Genetic10aEpithelial Cells10aFemale10aGene Expression Profiling10aGene Expression Regulation, Neoplastic10aGenome, Human10aHumans10aMicroRNAs10aNeoplasm Staging10aOvarian Neoplasms10aRibonuclease III10aRNA, Messenger10aSurvival Analysis1 aZhang, Lin1 aVolinia, Stefano1 aBonome, Tomas1 aCalin, George, Adrian1 aGreshock, Joel1 aYang, Nuo1 aLiu, Chang-Gong1 aGiannakakis, Antonis1 aAlexiou, Pangiotis1 aHasegawa, Kosei1 aJohnstone, Cameron, N1 aMegraw, Molly, S1 aAdams, Sarah1 aLassus, Heini1 aHuang, Jia1 aKaur, Sippy1 aLiang, Shun1 aSethupathy, Praveen1 aLeminen, Arto1 aSimossis, Victor, A1 aSandaltzopoulos, Raphael1 aNaomoto, Yoshio1 aKatsaros, Dionyssios1 aGimotty, Phyllis, A1 aDeMichele, Angela1 aHuang, Qihong1 aBützow, Ralf1 aRustgi, Anil, K1 aWeber, Barbara, L1 aBirrer, Michael, J1 aHatzigeorgiou, Artemis, G1 aCroce, Carlo, M1 aCoukos, George uhttp://megraw.cgrb.oregonstate.edu/node/328