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.
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.
Authors: Romy E Verbeek; Peter D Siersema; Fiebo J Ten Kate; Kees Fluiter; Rhonda F Souza; Frank P Vleggaar; Pauline Bus; Jantine W P M van Baal Journal: J Gastroenterol Date: 2013-08-17 Impact factor: 7.527
Authors: Katherine S Garman; Kouros Owzar; Elizabeth R Hauser; Kristen Westfall; Blair R Anderson; Rhonda F Souza; Anna Mae Diehl; Dawn Provenzale; Nicholas J Shaheen Journal: Dig Dis Sci Date: 2013-08-08 Impact factor: 3.199
Authors: Cameron M Smith; Michael Z Michael; David I Watson; Grace Tan; David St J Astill; Richard Hummel; Damian J Hussey Journal: BMC Gastroenterol Date: 2013-01-08 Impact factor: 3.067
Authors: Matteo Fassan; Stefano Volinia; Jeff Palatini; Marco Pizzi; Cecilia Fernandez-Cymering; Mariangela Balistreri; Stefano Realdon; Giorgio Battaglia; Rhonda Souza; Robert D Odze; Giovanni Zaninotto; Carlo M Croce; Massimo Rugge Md Facg Journal: Clin Transl Gastroenterol Date: 2013-05-16 Impact factor: 4.488