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

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.

• Authors: 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
• Journal: The Journal of pathology (J Pathol) Vol. 235 Issue 1 Pg. 25-36 (Jan 2015) ISSN: 1096-9896 [Electronic] England
• PMID: 25230372 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Chemical References

• Cadherins
• MIRN506 microRNA, human
• MicroRNAs
• Transcription Factors
• Vimentin

Topics

• Adult
• Aged
• Aged, 80 and over
• Cadherins (metabolism)
• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Cell Movement (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• MicroRNAs (genetics)
• Middle Aged
• Neoplasms, Glandular and Epithelial (diagnosis, genetics)
• Ovarian Neoplasms (diagnosis, genetics)
• Prognosis
• Transcription Factors (metabolism)
• Vimentin (metabolism)