Abstract
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-β-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-β signalling pathway in high-grade serous ovarian cancer.
| Original language | English |
|---|---|
| Article number | 2977 |
| Journal | Nature Communications |
| Volume | 5 |
| DOIs | |
| Publication status | Published - Jan 7 2014 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
- Medicine(all)
Cite this
MicroRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition. / Parikh, Aditya; Lee, Christine; Joseph, Peronne; Marchini, Sergio; Baccarini, Alessia; Kolev, Valentin; Romualdi, Chiara; Fruscio, Robert; Shah, Hardik; Wang, Feng; Mullokandov, Gavriel; Fishman, David; D'Incalci, Maurizio; Rahaman, Jamal; Kalir, Tamara; Redline, Raymond W.; Brown, Brian D.; Narla, Goutham; Difeo, Analisa.
In: Nature Communications, Vol. 5, 2977, 07.01.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial-mesenchymal transition
AU - Parikh, Aditya
AU - Lee, Christine
AU - Joseph, Peronne
AU - Marchini, Sergio
AU - Baccarini, Alessia
AU - Kolev, Valentin
AU - Romualdi, Chiara
AU - Fruscio, Robert
AU - Shah, Hardik
AU - Wang, Feng
AU - Mullokandov, Gavriel
AU - Fishman, David
AU - D'Incalci, Maurizio
AU - Rahaman, Jamal
AU - Kalir, Tamara
AU - Redline, Raymond W.
AU - Brown, Brian D.
AU - Narla, Goutham
AU - Difeo, Analisa
PY - 2014/1/7
Y1 - 2014/1/7
N2 - 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-β-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-β signalling pathway in high-grade serous ovarian cancer.
AB - 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-β-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-β signalling pathway in high-grade serous ovarian cancer.
UR - http://www.scopus.com/inward/record.url?scp=84891883182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891883182&partnerID=8YFLogxK
U2 - 10.1038/ncomms3977
DO - 10.1038/ncomms3977
M3 - Article
C2 - 24394555
AN - SCOPUS:84891883182
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2977
ER -