microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition

被引：247

作者：

Parikh, Aditya ^{[1
,2
]}

Lee, Christine ^{[1
,3
]}

Joseph, Peronne ^{[3
]}

Marchini, Sergio ^{[4
]}

Baccarini, Alessia ^{[1
]}

Kolev, Valentin ^{[5
]}

Romualdi, Chiara ^{[6
]}

Fruscio, Robert ^{[7
,8
]}

Shah, Hardik ^{[1
]}

Wang, Feng ^{[5
]}

Mullokandov, Gavriel ^{[1
]}

Fishman, David ^{[5
]}

D'Incalci, Maurizio ^{[4
]}

Rahaman, Jamal ^{[5
]}

Kalir, Tamara ^{[8
,9
]}

Redline, Raymond W. ^{[10
]}

Brown, Brian D. ^{[1
]}

Narla, Goutham ^{[1
,2
,3
,11
]}

Difeo, Analisa ^{[1
,3
]}

机构：

[1] Mt Sinai Sch Med, Dept Genet & Genom Sci, 1425 Madison Ave, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA

[3] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA

[4] IRCCS Ist Ric Farmacol Mario Negri, Dept Oncol, I-20156 Milan, Italy

[5] Mt Sinai Sch Med, Dept Obstet & Gynecol, New York, NY 10029 USA

[6] Univ Padua, Dept Biol, I-35121 Padua, Italy

[7] Univ Milano Bicocca, San Gerardo Hosp, Clin Obstet & Gynecol, I-20900 Monza, Italy

[8] MaNGO Grp, I-20156 Milan, Italy

[9] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA

[10] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH 44106 USA

[11] Case Western Q3 Reserve Univ, Dept Med, Inst Transformat Mol Med, Cleveland, OH 44106 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

TGF-BETA; EXPRESSION PROFILES; THERAPEUTIC TARGET; BREAST-CANCER; IDENTIFICATION; METASTASIS; BORDERLINE; RESISTANCE; BIOMARKER; MIR-181;

D O I：

10.1038/ncomms3977

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Ovarian cancer is a leading cause of cancer deaths among women. Effective targets to treat advanced epithelial ovarian cancer (EOC) and biomarkers to predict treatment response are still lacking because of the complexity of pathways involved in ovarian cancer progression. Here we show that miR-181a promotes TGF-beta-mediated epithelial-to-mesenchymal transition via repression of its functional target, Smad7. miR-181a and phosphorylated Smad2 are enriched in recurrent compared with matched-primary ovarian tumours and their expression is associated with shorter time to recurrence and poor outcome in patients with EOC. Furthermore, ectopic expression of miR-181a results in increased cellular survival, migration, invasion, drug resistance and in vivo tumour burden and dissemination. In contrast, miR-181a inhibition via decoy vector suppression and Smad7 re-expression results in significant reversion of these phenotypes. Combined, our findings highlight an unappreciated role for miR-181a, Smad7, and the TGF-beta signalling pathway in high-grade serous ovarian cancer.

引用

页数：16

共 41 条

[1]

Allred DC, 1998, MODERN PATHOL, V11, P155

[2]

Kinetic Analysis Reveals the Fate of a MicroRNA following Target Regulation in Mammalian Cells [J].

Baccarini, Alessia ;

Chauhan, Hemangini ;

Gardner, Thomas J. ;

Jayaprakash, Anitha D. ;

Sachidanandam, Ravi ;

Brown, Brian D. .

CURRENT BIOLOGY, 2011, 21 (05) :369-376

[3]

Baccarini A, 2010, METHODS MOL BIOL, V667, P215, DOI 10.1007/978-1-60761-811-9_15

[4]

Baldwin RL, 2003, CANCER RES, V63, P1413

[5]

Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[6]

Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer [J].

Cao, L. ;

Shao, M. ;

Schilder, J. ;

Guise, T. ;

Mohammad, K. S. ;

Matei, D. .

ONCOGENE, 2012, 31 (20) :2521-2534

[7]

KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers [J].

Corson, TW ;

Huang, A ;

Tsao, MS ;

Gallie, BL .

ONCOGENE, 2005, 24 (30) :4741-4753

[8]

MicroRNAs in ovarian carcinomas [J].

Dahiya, Neetu ;

Morin, Patrice J. .

[9]

MicroRNA Expression and Identification of Putative miRNA Targets in Ovarian Cancer [J].

Dahiya, Neetu ;

Sherman-Baust, Cheryl A. ;

Wang, Tian-Li ;

Davidson, Ben ;

Shih, Ie-Ming ;

Zhang, Yongqing ;

Wood, William, III ;

Becker, Kevin G. ;

Morin, Patrice J. .

PLOS ONE, 2008, 3 (06)

[10]

Expression of cadherins in benign, borderline, and malignant ovarian epithelial tumors: A clinicopathologic study of 60 cases [J].

Darai, E ;

Scoazec, JY ;

WalkerCombrouze, F ;

MlikaCabanne, N ;

Feldmann, G ;

Madelenat, P ;

Potet, F .

HUMAN PATHOLOGY, 1997, 28 (08) :922-928

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