Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1

T. K H Chung, T. S. Lau, T. H. Cheung, S. F. Yim, K. W K Lo, N. S S Siu, L. K Y Chan, M. Y. Yu, J. Kwong, G. Doran, L. M. Barroilhet, A. S W Ng, R. R Y Wong, V. W. Wang, S. C. Mok, David I Smith, R. S. Berkowitz, Y. F. Wong

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3′-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.

Original languageEnglish (US)
Pages (from-to)1036-1045
Number of pages10
JournalInternational Journal of Cancer
Volume130
Issue number5
DOIs
StatePublished - Mar 1 2012

Fingerprint

Endometrial Neoplasms
MicroRNAs
Phenotype
Neoplasms
RNA Stability
3' Untranslated Regions
European Union
Luciferases
Oncogenes
Extracellular Matrix
Transfection
Real-Time Polymerase Chain Reaction
Biomarkers
Binding Sites
Neoplasm Metastasis

Keywords

  • endometrial cancer
  • FOXC1
  • microRNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chung, T. K. H., Lau, T. S., Cheung, T. H., Yim, S. F., Lo, K. W. K., Siu, N. S. S., ... Wong, Y. F. (2012). Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1. International Journal of Cancer, 130(5), 1036-1045. https://doi.org/10.1002/ijc.26060

Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1. / Chung, T. K H; Lau, T. S.; Cheung, T. H.; Yim, S. F.; Lo, K. W K; Siu, N. S S; Chan, L. K Y; Yu, M. Y.; Kwong, J.; Doran, G.; Barroilhet, L. M.; Ng, A. S W; Wong, R. R Y; Wang, V. W.; Mok, S. C.; Smith, David I; Berkowitz, R. S.; Wong, Y. F.

In: International Journal of Cancer, Vol. 130, No. 5, 01.03.2012, p. 1036-1045.

Research output: Contribution to journalArticle

Chung, TKH, Lau, TS, Cheung, TH, Yim, SF, Lo, KWK, Siu, NSS, Chan, LKY, Yu, MY, Kwong, J, Doran, G, Barroilhet, LM, Ng, ASW, Wong, RRY, Wang, VW, Mok, SC, Smith, DI, Berkowitz, RS & Wong, YF 2012, 'Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1', International Journal of Cancer, vol. 130, no. 5, pp. 1036-1045. https://doi.org/10.1002/ijc.26060
Chung, T. K H ; Lau, T. S. ; Cheung, T. H. ; Yim, S. F. ; Lo, K. W K ; Siu, N. S S ; Chan, L. K Y ; Yu, M. Y. ; Kwong, J. ; Doran, G. ; Barroilhet, L. M. ; Ng, A. S W ; Wong, R. R Y ; Wang, V. W. ; Mok, S. C. ; Smith, David I ; Berkowitz, R. S. ; Wong, Y. F. / Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1. In: International Journal of Cancer. 2012 ; Vol. 130, No. 5. pp. 1036-1045.
@article{78874d4f7732458b8780d73a7cb8c757,
title = "Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1",
abstract = "MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3′-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.",
keywords = "endometrial cancer, FOXC1, microRNA",
author = "Chung, {T. K H} and Lau, {T. S.} and Cheung, {T. H.} and Yim, {S. F.} and Lo, {K. W K} and Siu, {N. S S} and Chan, {L. K Y} and Yu, {M. Y.} and J. Kwong and G. Doran and Barroilhet, {L. M.} and Ng, {A. S W} and Wong, {R. R Y} and Wang, {V. W.} and Mok, {S. C.} and Smith, {David I} and Berkowitz, {R. S.} and Wong, {Y. F.}",
year = "2012",
month = "3",
day = "1",
doi = "10.1002/ijc.26060",
language = "English (US)",
volume = "130",
pages = "1036--1045",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1

AU - Chung, T. K H

AU - Lau, T. S.

AU - Cheung, T. H.

AU - Yim, S. F.

AU - Lo, K. W K

AU - Siu, N. S S

AU - Chan, L. K Y

AU - Yu, M. Y.

AU - Kwong, J.

AU - Doran, G.

AU - Barroilhet, L. M.

AU - Ng, A. S W

AU - Wong, R. R Y

AU - Wang, V. W.

AU - Mok, S. C.

AU - Smith, David I

AU - Berkowitz, R. S.

AU - Wong, Y. F.

PY - 2012/3/1

Y1 - 2012/3/1

N2 - MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3′-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.

AB - MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3′-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.

KW - endometrial cancer

KW - FOXC1

KW - microRNA

UR - http://www.scopus.com/inward/record.url?scp=84155168994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84155168994&partnerID=8YFLogxK

U2 - 10.1002/ijc.26060

DO - 10.1002/ijc.26060

M3 - Article

VL - 130

SP - 1036

EP - 1045

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 5

ER -