MiR-506 inhibits multiple targets in the epithelial-to- mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer

Yan Sun, Limei Hu, Hong Zheng, Marina Bagnoli, Yuhong Guo, Rajesha Rupaimoole, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Ping Ji, Kexin Chen, Anil K. Sood, Delia Mezzanzanica, Jinsong Liu, Baocun Sun, Wei Zhang

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Extensive investigations have shown that miRNAs are important regulators of epithelial-to-mesenchymal transition (EMT), mainly targeting the transcriptional repressors of E-cadherin (E-cad). Less is known about the post-transcriptional regulation of vimentin or N-cadherin (N-cad) in EMT. Our previous study identified miR-506 as a key EMT inhibitor through directly targeting the E-cad transcriptional repressor SNAI2. In this study, we provide evidence that miR-506 simultaneously suppresses vimentin and N-cad. The knockdown of vimentin using siRNA reversed EMT, suppressed cell migration and invasion, and increased E-cad expression on the cell membrane in epithelial ovarian cancer (EOC) cells. In a set of tissue microarrays that included 204 EOCs of all major subtypes (eg serous, endometrioid, clear cell, and mucinous), miR-506 was positively correlated with E-cad and negatively correlated with vimentin and N-cad in all subtypes of EOC. A high level of miR-506 was positively associated with early FIGO stage and longer survival in EOC. Introduction of miR-506, mediated by nanoparticle delivery, in EOC orthotopic mouse models resulted in decreased vimentin, N-cad, and SNAI2 expression and increased E-cad expression; it also suppressed the dissemination of EOC cells. Thus, miR-506 represents a new class of miRNA that regulates both E-cad and vimentin/N-cad in the suppression of EMT and metastasis.

Original languageEnglish (US)
Pages (from-to)25-36
Number of pages12
JournalJournal of Pathology
Volume235
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Epithelial ovarian cancer
  • Epithelial-to-mesenchymal transition
  • N-cadherin
  • Nanoparticle
  • Vimentin
  • miR-506

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Sun, Y., Hu, L., Zheng, H., Bagnoli, M., Guo, Y., Rupaimoole, R., Rodriguez-Aguayo, C., Lopez-Berestein, G., Ji, P., Chen, K., Sood, A. K., Mezzanzanica, D., Liu, J., Sun, B., & Zhang, W. (2015). MiR-506 inhibits multiple targets in the epithelial-to- mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer. Journal of Pathology, 235(1), 25-36. https://doi.org/10.1002/path.4443