title: 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.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Limei
authors.initials: L
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Marina
authors.initials: M
authors.lastname: Bagnoli
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Guo
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Delia
authors.initials: D
authors.lastname: Mezzanzanica
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; C561508:MIRN506 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D014746:Vimentin
keywords: N-cadherin; epithelial ovarian cancer; epithelial-to-mesenchymal transition; miR-506; nanoparticle; vimentin