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

Research output: Contribution to journalArticle

34 Scopus citations

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 1 2013

    Fingerprint

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., Kate, F. J. W. T., Vleggaar, F. P., & 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