Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer.
Yan Sun,Fei Guo,Marina Bagnoli,Feng Xia Xue,Baocun Sun,Ilya Shmulevich,Delia Mezzanzanica,Ke Xin Chen,Anil K. Sood,Da Yang,Wei Zhang +10 more
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TLDR
It is found that integrating mRNA and microRNA data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer, consisting of 8 major miRNAs and 214 mRNAs.Abstract:
Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This “paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.read more
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TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
Journal ArticleDOI
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TL;DR: The results indicate that miRNAs are extensively involved in cancer pathogenesis of solid tumors and support their function as either dominant or recessive cancer genes.
Integrated genomic analyses of ovarian carcinoma
Daphne W. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,Mei Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Douglas A. Levine,Gordon B. Mills,Carolyn A. Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,Jennifer Drummond,Gerald R. Fowler,Preethi H. Gunaratne,Alicia Hawes,Christie Kovar,Lora Lewis,Margaret B. Morgan,Irene Newsham,Jireh Santibanez,Jeffrey G. Reid,Lisa R. Trevino,Yuan Qing Wu,Min Wang,Donna Muzny,D Wheeler,Richard A. Gibbs,Gad Getz,Michael S. Lawrence,Kristian Cibulskis,Andrey Sivachenko,Carrie Sougnez,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,T. J. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,Michelle D O'Laughlin,David J. Dooling,Linnea Fulton,Rachel Abbott,Nathan D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Heather K. Schmidt,Joelle Kalicki,Kimberly D. Delehaunty,Catrina Fronick,Ryan Demeter,Linda S. Cook,John W. Wallis,Ling Lin,Vincent Magrini,Jennifer S. Hodges,James M. Eldred,Shaleigh Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,Roeland Verhaak,Suzie Carter,Craig H. Mermel,Gordon Saksena,Huy V. Nguyen,Robert C. Onofrio,Diana D. Hubbard,Sonal Gupta,Andrew Crenshaw,Alex H. Ramos,Lynda Chin,Alexei Protopopov,Juinhua Zhang,T. M. Kim,Ilana Perna,Yonghong Xiao,Hailei Zhang,Gang Ren,Narayanan Sathiamoorthy,Richard W. Park,Eunjung Lee,Peter J. Park,Raju Kucherlapati,Devin Absher,Lindsay L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,Leslie Cope,James G. Herman,Hui Shen,Daniel J. Weisenberger,Houtan Noushmehr,Fei Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,Jonathan D. Buckley,Stephen B. Baylin,P. Spellman,Elizabeth Purdom,Pierre Neuvial,Henrik Bengtsson,Lakshmi Jakkula,Steffen Durinck,Junhong Han,Shannon Dorton,Henry Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,John G. Conboy,Bahram Parvin,Heidi S. Feiler,Terence P. Speed,Joe W. Gray,Nicholas D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Laetitia Borsu,Alex E. Lash,Cameron Brennan,Agnes Viale,Chris Sander,M. Ladanyi,Katherine A. Hoadley,Shaowu Meng,Ying Du,Yan Shi,Lulin Li,Yidi J. Turman,D. Zang,E. B. Helms,Saianand Balu,Xiang Zhou,Jane Y. Wu,Michael D. Topal,David N. Hayes,Charles M. Perou,Junihua Zhang,Chaowei Wu,Sachet A. Shukla,Andrey Sivachenko,Rui Jing,Yingkai Liu,Michael S. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,Adam B. Olshen,Boris Reva,Yevgeniy Antipin,Ronglai Shen,Parminder K. Mankoo,Rachael Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,John Zachary Sanborn,Charles J. Vaske,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Matthew D. Wilkerson,Nianxiang Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,Troy Shelton,Dirk Grimm,Martha Hatfield,Shannon R. Morris,Peggy Yena,P. Rhodes,Mark E. Sherman,Joseph Paulauskis,S. Millis,Ari B. Kahn,John M. Greene,Robert Sfeir,Mark A. Jensen,John W. Chen,Jon Whitmore,Shelley Alonso,Justin T. Jordan,Anna L. Chu,Jinghui Zhang,Anna D. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jessica L. Peterson,E. Thomson +261 more
TL;DR: The Cancer Genome Atlas project has analyzed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours as mentioned in this paper.
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The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.
Philip A. Gregory,Andrew G. Bert,Emily L. Paterson,Simon C. Barry,Anna Tsykin,Gelareh Farshid,Mathew A. Vadas,Mathew A. Vadas,Yeesim Khew-Goodall,Gregory J. Goodall +9 more
TL;DR: It is found that all five members of the microRNA-200 family were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)-β or to ectopic expression of the protein tyrosine phosphatase Pez, suggesting that downregulation of themicroRNAs may be an important step in tumour progression.
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TL;DR: Tarin et al. as discussed by the authors described the process of epithelial-mesenchymal transition (EMT) as a defining structural feature of organ development and discussed its role in cancer and fibrosis, as well as identifying new markers to facilitate the observation of EMT in vivo.
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