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

56 Citations (Scopus)

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
Pages (from-to)25-36
Number of pages12
JournalJournal of Pathology
Volume235
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Epithelial-Mesenchymal Transition
Vimentin
Cadherins
MicroRNAs
Nanoparticles
Small Interfering RNA
Cell Movement
Ovarian epithelial cancer
Cell Membrane
Neoplasm Metastasis

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

MiR-506 inhibits multiple targets in the epithelial-to- mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer. / Sun, Yan; Hu, Limei; Zheng, Hong; Bagnoli, Marina; Guo, Yuhong; Rupaimoole, Rajesha; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Ji, Ping; Chen, Kexin; Sood, Anil K.; Mezzanzanica, Delia; Liu, Jinsong; Sun, Baocun; Zhang, Wei.

In: Journal of Pathology, Vol. 235, No. 1, 01.01.2015, p. 25-36.

Research output: Contribution to journalArticle

Sun, Y, Hu, L, Zheng, H, Bagnoli, M, Guo, Y, Rupaimoole, R, Rodriguez-Aguayo, C, Lopez-Berestein, G, Ji, P, Chen, K, Sood, AK, 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, vol. 235, no. 1, pp. 25-36. https://doi.org/10.1002/path.4443
Sun, Yan ; Hu, Limei ; Zheng, Hong ; Bagnoli, Marina ; Guo, Yuhong ; Rupaimoole, Rajesha ; Rodriguez-Aguayo, Cristian ; Lopez-Berestein, Gabriel ; Ji, Ping ; Chen, Kexin ; Sood, Anil K. ; Mezzanzanica, Delia ; Liu, Jinsong ; Sun, Baocun ; Zhang, Wei. / MiR-506 inhibits multiple targets in the epithelial-to- mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer. In: Journal of Pathology. 2015 ; Vol. 235, No. 1. pp. 25-36.
@article{7f8ba8776c20475fb0dc0d1971f92e24,
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.",
keywords = "Epithelial ovarian cancer, Epithelial-to-mesenchymal transition, miR-506, N-cadherin, Nanoparticle, Vimentin",
author = "Yan Sun and Limei Hu and Hong Zheng and Marina Bagnoli and Yuhong Guo and Rajesha Rupaimoole and Cristian Rodriguez-Aguayo and Gabriel Lopez-Berestein and Ping Ji and Kexin Chen and Sood, {Anil K.} and Delia Mezzanzanica and Jinsong Liu and Baocun Sun and Wei Zhang",
year = "2015",
month = "1",
day = "1",
doi = "10.1002/path.4443",
language = "English",
volume = "235",
pages = "25--36",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - MiR-506 inhibits multiple targets in the epithelial-to- mesenchymal transition network and is associated with good prognosis in epithelial ovarian cancer

AU - Sun, Yan

AU - Hu, Limei

AU - Zheng, Hong

AU - Bagnoli, Marina

AU - Guo, Yuhong

AU - Rupaimoole, Rajesha

AU - Rodriguez-Aguayo, Cristian

AU - Lopez-Berestein, Gabriel

AU - Ji, Ping

AU - Chen, Kexin

AU - Sood, Anil K.

AU - Mezzanzanica, Delia

AU - Liu, Jinsong

AU - Sun, Baocun

AU - Zhang, Wei

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Epithelial ovarian cancer

KW - Epithelial-to-mesenchymal transition

KW - miR-506

KW - N-cadherin

KW - Nanoparticle

KW - Vimentin

UR - http://www.scopus.com/inward/record.url?scp=84916201333&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84916201333&partnerID=8YFLogxK

U2 - 10.1002/path.4443

DO - 10.1002/path.4443

M3 - Article

VL - 235

SP - 25

EP - 36

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 1

ER -