microRNA-145 in Barrett's oesophagus: regulating BMP4 signalling via GATA6

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

doi:10.1136/gutjnl-2011-301061

Cited by 47 publications

(52 citation statements)

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“…Several of the miRNAs identified as highly expressed in BE are linked to the intestinal phenotype, and are expressed in the mouse small intestine [40]. Logically, this similarity between BE and intestinal phenotype makes sense, and recently, investigators have begun to assess the role of specific miRNAs (such as miR-145) in the development of BE [41]. Some of the miRNAs that increase in BE then decrease in some EACs as the cancer phenotype develops.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

et al. 2013

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Background Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed. Aims We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett’s esophagus (BE), and EAC. Methods We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n=11), BE (n=14), and high-grade dysplasia (HGD)/EAC (n=11). RNA was assessed using microarrays representing 847 human microRNAs followed by qRT-PCR verification of nine microRNAs. In a second cohort (n=18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs. Results After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo. Conclusions These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

et al. 2013

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“…In particular, miR-143, miR-145 and miR-215 are considered tumor suppressors, downregulated in EAC probably due to additional molecular alterations that occur during carcinogenesis, such as loss of p53 homozygosity with consequent alteration of the functionality and ability that p53 exerts on the regulation of these three miRNAs [23, 34–36]. In addition, the analysis of miR-145, most upregulated in BE compared to CLO, is consistent with its role in the differentiation towards the intestinal metaplasia via the feedback circuit with BMP-4, which is reported to be overexpressed in BE [37]. In the present study, miR-145 is also up-regulated in the CLO, although to a lesser extent.…”

Section: Discussionmentioning

confidence: 84%

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

et al. 2016

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Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined oesophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients.

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“…Similarly, GATA6 expression is also increased in BE lesions compared to normal esophageal epithelium [57] and the overexpression of GATA6, together with FGFR2IIb, has been found to increase the anchorage-independent growth of the BE cell line CP-A [58] . Conflicting results show that upregulated miR-145 in BE lesions downregulates GATA6 and inhibits proliferation in nonneoplastic esophageal Het-1A cells [59] . Interestingly, it is thought that the binding of FOXA and GATA factors, which are pioneer transcription factors, opens up and reshapes closed (hetero)chromatin [60] .…”

Section: Cdx-2 As a Potential Key Regulator During Be Developmentmentioning

confidence: 91%

Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus

Ahrens

Lutz²,

Laßmann³

et al. 2016

Pathobiology

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Barrett's esophagus (BE) is defined as metaplasia of the esophageal squamous epithelium with multiple cell layers into a single layer of intestinal columnar epithelial cells - or, in other words, skyscrapers are turned into town houses. The underlying pathomechanism(s) and the cell of origin of BE lesions have not been defined yet. However, four potential hypotheses for BE development have been suggested. The morphological changes during BE development are associated with rather well-described aberrant gene/protein expression patterns. However, the potential key regulators of this conversion process are still unclear. The process of metaplastic conversion is difficult to monitor in a spatiotemporal manner in vitro, and robust models are lacking. There is therefore a need for novel experimental systems. This review focuses on potential key regulators, microenvironmental influences, epigenetic alterations and experimental research systems related to BE.

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microRNA-145 in Barrett's oesophagus: regulating BMP4 signalling via GATA6

Abstract: These results imply that miRNA-145 indirectly targets BMP4 via GATA6 and is potentially involved in the development of BE.

Cited by 47 publications

References 47 publications

MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Turning Skyscrapers into Town Houses: Insights into Barrett's Esophagus

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