MicroRNA-145 in Barrett's oesophagus: Regulating BMP4 signalling via GATA6

Jantine W P M Van Baal, Romy E. Verbeek, Pauline Bus, Matteo Fassan, Rhonda F. Souza, Massimo Rugge, Fiebo J W Ten Kate, Frank P. Vleggaar, Peter D. Siersema

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Abstract

Objective Barrett's oesophagus (BE) is a metaplastic condition of the distal oesophagus which predisposes to oesophageal adenocarcinoma (EAC). It has been suggested that microRNAs (miRNAs) are involved in the process of development of BE and EAC; however, few functional miRNA data are available. The aim of the study was to perform a tissue-specific miRNA profile and, based on this, to examine the function of miRNA-145 in the oesophagus. Design miRNA expression profiling using microarray analysis in EAC, BE and normal squamous epithelium of the oesophagus (SQ) was performed and validated using real-time PCR in samples from 15 patients and in situ hybridisation in samples from 10 patients. The proliferative effect of miRNA-145 precursor transfection in the SQ (HET-1A) and BE cell line (BAR-T) was measured. Downstream targets of miRNA-145 were determined by analysing mRNA and protein expression from miRNA-145 transfected cells. Results Three unique miRNA expression profiles were found in tissue from EAC, BE and SQ, which showed that miRNA-145 was upregulated in BE compared with EAC and SQ. Overexpression of miRNA-145 in HET-1A and BAR-T cells reduced cell proliferation and inhibited GATA6, BMP4 and SOX9 mRNA expression. Furthermore, altered BMP4 signalling was observed in vitro on miRNA-145 overexpression. These effects were blocked when cells were co-transfected with a miRNA- 145 specific inhibitor. Additionally, BMP4 incubation of HET-1A cells altered miRNA-145 and GATA6 expression over time. Conclusion These results imply that miRNA-145 indirectly targets BMP4 via GATA6 and is potentially involved in the development of BE.

Original languageEnglish (US)
Pages (from-to)664-675
Number of pages12
JournalGut
Volume62
Issue number5
DOIs
StatePublished - May 2013

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Barrett Esophagus
MicroRNAs
Esophagus
Messenger RNA
Microarray Analysis
In Situ Hybridization

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Van Baal, J. W. P. M., Verbeek, R. E., Bus, P., Fassan, M., Souza, R. F., Rugge, M., ... Siersema, P. D. (2013). MicroRNA-145 in Barrett's oesophagus: Regulating BMP4 signalling via GATA6. Gut, 62(5), 664-675. https://doi.org/10.1136/gutjnl-2011-301061

MicroRNA-145 in Barrett's oesophagus : Regulating BMP4 signalling via GATA6. / Van Baal, Jantine W P M; Verbeek, Romy E.; Bus, Pauline; Fassan, Matteo; Souza, Rhonda F.; Rugge, Massimo; Kate, Fiebo J W Ten; Vleggaar, Frank P.; Siersema, Peter D.

In: Gut, Vol. 62, No. 5, 05.2013, p. 664-675.

Research output: Contribution to journalArticle

Van Baal, JWPM, Verbeek, RE, Bus, P, Fassan, M, Souza, RF, Rugge, M, Kate, FJWT, Vleggaar, FP & Siersema, PD 2013, 'MicroRNA-145 in Barrett's oesophagus: Regulating BMP4 signalling via GATA6', Gut, vol. 62, no. 5, pp. 664-675. https://doi.org/10.1136/gutjnl-2011-301061
Van Baal JWPM, Verbeek RE, Bus P, Fassan M, Souza RF, Rugge M et al. MicroRNA-145 in Barrett's oesophagus: Regulating BMP4 signalling via GATA6. Gut. 2013 May;62(5):664-675. https://doi.org/10.1136/gutjnl-2011-301061
Van Baal, Jantine W P M ; Verbeek, Romy E. ; Bus, Pauline ; Fassan, Matteo ; Souza, Rhonda F. ; Rugge, Massimo ; Kate, Fiebo J W Ten ; Vleggaar, Frank P. ; Siersema, Peter D. / MicroRNA-145 in Barrett's oesophagus : Regulating BMP4 signalling via GATA6. In: Gut. 2013 ; Vol. 62, No. 5. pp. 664-675.
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abstract = "Objective Barrett's oesophagus (BE) is a metaplastic condition of the distal oesophagus which predisposes to oesophageal adenocarcinoma (EAC). It has been suggested that microRNAs (miRNAs) are involved in the process of development of BE and EAC; however, few functional miRNA data are available. The aim of the study was to perform a tissue-specific miRNA profile and, based on this, to examine the function of miRNA-145 in the oesophagus. Design miRNA expression profiling using microarray analysis in EAC, BE and normal squamous epithelium of the oesophagus (SQ) was performed and validated using real-time PCR in samples from 15 patients and in situ hybridisation in samples from 10 patients. The proliferative effect of miRNA-145 precursor transfection in the SQ (HET-1A) and BE cell line (BAR-T) was measured. Downstream targets of miRNA-145 were determined by analysing mRNA and protein expression from miRNA-145 transfected cells. Results Three unique miRNA expression profiles were found in tissue from EAC, BE and SQ, which showed that miRNA-145 was upregulated in BE compared with EAC and SQ. Overexpression of miRNA-145 in HET-1A and BAR-T cells reduced cell proliferation and inhibited GATA6, BMP4 and SOX9 mRNA expression. Furthermore, altered BMP4 signalling was observed in vitro on miRNA-145 overexpression. These effects were blocked when cells were co-transfected with a miRNA- 145 specific inhibitor. Additionally, BMP4 incubation of HET-1A cells altered miRNA-145 and GATA6 expression over time. Conclusion These results imply that miRNA-145 indirectly targets BMP4 via GATA6 and is potentially involved in the development of BE.",
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T1 - MicroRNA-145 in Barrett's oesophagus

T2 - Regulating BMP4 signalling via GATA6

AU - Van Baal, Jantine W P M

AU - Verbeek, Romy E.

AU - Bus, Pauline

AU - Fassan, Matteo

AU - Souza, Rhonda F.

AU - Rugge, Massimo

AU - Kate, Fiebo J W Ten

AU - Vleggaar, Frank P.

AU - Siersema, Peter D.

PY - 2013/5

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N2 - Objective Barrett's oesophagus (BE) is a metaplastic condition of the distal oesophagus which predisposes to oesophageal adenocarcinoma (EAC). It has been suggested that microRNAs (miRNAs) are involved in the process of development of BE and EAC; however, few functional miRNA data are available. The aim of the study was to perform a tissue-specific miRNA profile and, based on this, to examine the function of miRNA-145 in the oesophagus. Design miRNA expression profiling using microarray analysis in EAC, BE and normal squamous epithelium of the oesophagus (SQ) was performed and validated using real-time PCR in samples from 15 patients and in situ hybridisation in samples from 10 patients. The proliferative effect of miRNA-145 precursor transfection in the SQ (HET-1A) and BE cell line (BAR-T) was measured. Downstream targets of miRNA-145 were determined by analysing mRNA and protein expression from miRNA-145 transfected cells. Results Three unique miRNA expression profiles were found in tissue from EAC, BE and SQ, which showed that miRNA-145 was upregulated in BE compared with EAC and SQ. Overexpression of miRNA-145 in HET-1A and BAR-T cells reduced cell proliferation and inhibited GATA6, BMP4 and SOX9 mRNA expression. Furthermore, altered BMP4 signalling was observed in vitro on miRNA-145 overexpression. These effects were blocked when cells were co-transfected with a miRNA- 145 specific inhibitor. Additionally, BMP4 incubation of HET-1A cells altered miRNA-145 and GATA6 expression over time. Conclusion These results imply that miRNA-145 indirectly targets BMP4 via GATA6 and is potentially involved in the development of BE.

AB - Objective Barrett's oesophagus (BE) is a metaplastic condition of the distal oesophagus which predisposes to oesophageal adenocarcinoma (EAC). It has been suggested that microRNAs (miRNAs) are involved in the process of development of BE and EAC; however, few functional miRNA data are available. The aim of the study was to perform a tissue-specific miRNA profile and, based on this, to examine the function of miRNA-145 in the oesophagus. Design miRNA expression profiling using microarray analysis in EAC, BE and normal squamous epithelium of the oesophagus (SQ) was performed and validated using real-time PCR in samples from 15 patients and in situ hybridisation in samples from 10 patients. The proliferative effect of miRNA-145 precursor transfection in the SQ (HET-1A) and BE cell line (BAR-T) was measured. Downstream targets of miRNA-145 were determined by analysing mRNA and protein expression from miRNA-145 transfected cells. Results Three unique miRNA expression profiles were found in tissue from EAC, BE and SQ, which showed that miRNA-145 was upregulated in BE compared with EAC and SQ. Overexpression of miRNA-145 in HET-1A and BAR-T cells reduced cell proliferation and inhibited GATA6, BMP4 and SOX9 mRNA expression. Furthermore, altered BMP4 signalling was observed in vitro on miRNA-145 overexpression. These effects were blocked when cells were co-transfected with a miRNA- 145 specific inhibitor. Additionally, BMP4 incubation of HET-1A cells altered miRNA-145 and GATA6 expression over time. Conclusion These results imply that miRNA-145 indirectly targets BMP4 via GATA6 and is potentially involved in the development of BE.

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