MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg

Department of Pathology, Mount Sinai Medical Center, New York, NY 10029, USA.
The Journal of thoracic and cardiovascular surgery (Impact Factor: 4.17). 03/2008; 135(2):255-60; discussion 260. DOI: 10.1016/j.jtcvs.2007.08.055
Source: PubMed


Expression of microRNAs by array analysis provides unique profiles for classifying tissues and tumors. The purpose of our study was to examine microRNA expression in Barrett esophagus and esophageal cancer to identify potential markers for disease progression.
MicroRNA was isolated from 35 frozen specimens (10 adenocarcinoma, 10 squamous cell carcinoma, 9 normal epithelium, 5 Barrett esophagus, and 1 high-grade dysplasia). MicroRNA expression was analyzed with Ambion bioarrays (Ambion, Austin, Tex) containing 328 human microRNA probes.
Unsupervised hierarchic clustering resulted in four major branches corresponding with four histologic groups. One branch consisted of 7 normal epithelium samples and 1 squamous cell carcinoma sample. The second branch consisted of 7 squamous cell carcinoma samples and 1 normal epithelium sample. The third branch contained 4 Barrett esophagus samples and 1 squamous cell carcinoma sample. The fourth contained all the adenocarcinoma samples and 1 sample each of Barrett esophagus, normal epithelium, squamous cell carcinoma, and high-grade dysplasia. Supervised classification with principal component analysis determined that the normal epithelium samples were more similar to the squamous cell carcinoma tumors, whereas the Barrett esophagus samples were more similar to adenocarcinoma. Pairwise comparisons between sample types revealed microRNAs that may be markers of tumor progression. Both mir_203 and mir_205 were expressed 2- to 10-fold lower in squamous cell carcinoma and adenocarcinomas than in normal epithelium. The mir_21 expression was 3- to 5-fold higher in both tumors than in normal epithelium. Prediction analysis of microarray classified 3 Barrett esophagus samples as Barrett esophagus, 1 as adenocarcinoma, and 1 as normal epithelium.
Expression profiles of miRNA distinguish esophageal tumor histology and can discriminate normal tissue from tumor. MicroRNA expression may prove useful for identifying patients with Barrett esophagus at high risk for progression to adenocarcinoma.

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Available from: Liqiang Xi, Jan 07, 2014
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    • "Also, by analysing samples from 45 American patients diagnosed with oesophageal adenocarcinoma using qPCR Feber et al. (2011) found that there was significantly lower levels of miR- 143 and miR-145 expressed in oesophageal adenocarcinomas compared to normal squamous mucosae. Feber et al. (2008) used 10 oesophageal adenocarcinomas, 5 Barrett's oesophagus, 1 high grade glandular dysplasia and 9 normal oesophageal mucosae from American patients to study the expressions of miRNAs by microarray analyses. It was found that miR-194, miR-21, miR-192, miR-93 and miR-200c were significantly up-regulated whereas miR-205 and miR-203 were significantly down-regulated in oesophageal adenocarcinoma compared to normal oesophageal mucosa. "
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    ABSTRACT: Aberrant expressions of micro-ribonucleic acids (miRs) are closely associated with the pathogenesis in many human cancers. In oesophageal adenocarcinomas, altered expressions of different sets of miRs are noted to be associated with the development of adenocarcinoma from Barrett's oesophagus. In different studies, miRs such as miR-192, miR-196 and miR-21 were frequently noted to up-regulated whereas miR-203, miR-205 and miR-let-7 were commonly down-regulated during the development of Barrett's oesophagus to oesophageal adenocarcinoma. In addition, changes in the expression of miRs are associated with the predication of metastasis, prognosis and response to chemo-radiation in the patients with oesophageal adenocarcinoma. Experimental studies in manipulating the miRs in cancer cell lines could provide hints for therapeutics for the cancer. However, the number of studies reported on these aspects of oesophageal adenocarcinoma was limited and the miRs noted needed to be confirmed by additional studies. Overall, the mechanisms of involvements of miRs in pathogenesis and progression of oesophageal adenocarcinoma are complex. Although miRs have the potential to act as prognostic and clinical biomarkers for cancer therapy in oesophageal adenocarcinoma, more works in larger populations and clinical trials are needed to validate these clinical implications. Copyright © 2015. Published by Elsevier Inc.
    Experimental and Molecular Pathology 03/2015; 98(3). DOI:10.1016/j.yexmp.2015.03.002 · 2.71 Impact Factor
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    • "Numerous studies showed that miR-203 has tumor suppressor functions in various cancer types (Gaur et al., 2007; Bueno et al., 2008; Feber et al., 2008) as its expression was abolished by chromosomal deletion or promoter CpG island hypermethylation in cancer cells (Bueno et al., 2008; Furuta et al., 2010). MiR-203 transcription was specifically repressed by the epithelial–mesenchymal translation (EMT) activator ZEB1, contributing to pancreatic and colorectal cancer cell invasive and metastatic behavior (Wellner et al., 2009). "
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    ABSTRACT: Long non-coding RNAs (lncRNAs) are ubiquitously expressed RNA molecules of more than 200 nucleotides without substantial ORFs. LncRNAs could act as epigenetic regulators of gene expression affecting transcription, mRNA stability and transport, and translation, although, precise functions have been attributed to only few of them. Competing endogenous RNAs (ceRNAs) represent one recently emerged type of functional lncRNAs that share microRNA recognition sequences with mRNAs and may compete for microRNA binding and thus affect regulation and function of target mRNAs. We studied the epigenetic regulation of the BARD1 gene. The BARD1 protein acts as tumor suppressor with BRCA1. In cancer, mRNAs encoding the tumor suppressor full length BARD1 are often down-regulated while the expression of oncogenic truncated isoforms is boosted. We found that the BARD1 3'UTR is almost 3000 nt long and harbors a large number of microRNA binding elements. In addition we discovered a novel lncRNA, BARD1 9'L, which is transcribed from an alternative promoter in intron 9 of the BARD1 gene and shares part of the 3'UTR with the protein coding BARD1 mRNAs. We demonstrate with the example of two microRNAs, miR-203 and miR-101, that they down-regulate the expression of FL BARD1 and cancer-associated BARD1 mRNAs, and that BARD1 9'L counteracts the effect of miR-203 and miR-101, As BARD1 9'L is abnormally over-expressed in human cancers, we suggest it might be a tumor promoting factor and treatment target.
    The International Journal of Biochemistry & Cell Biology 07/2014; 54. DOI:10.1016/j.biocel.2014.06.018 · 4.05 Impact Factor
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    • "ee isoforms in ESCC cell lines and patient samples , and provide evidence to support the differential expression of those three isoforms in different cancers . Downregulation of miR - 203 has been reported in a number of different cancers including ESCC ( Castilla et al . , 2011 ; Chen et al . , 2011 ; Chiang et al . , 2011 ; Chim et al . , 2011 ; Feber et al . , 2008 ) . The loss of function caused by miR - 203 dysregulation is involved in more aggressive tumor behaviors . In our in vitro EMT model , miR - 203 was dramatically decreased in response to EGF treatment ( Fig . 5A ) , which is consistent with the observations by Sonkoly and colleagues ( Sonkoly et al . , 2010 ) . In particular , miR - 20"
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is a developmental program, which is associated with esophageal squamous cell carcinoma (ESCC) progression and metastasis. Recently, C/EBPβ is reported to be an EMT inducer in cancer. However, the detailed molecular mechanisms remain unclear. Here we report for the first time, that the truncated C/EBPβ LIP isoform was abnormally overexpressed and correlated with cancer metastasis in clinical specimens of human ESCC. Furthermore, we demonstrate that C/EBPβ LIP mediates epithelial growth factor (EGF) - induced EMT and increases migration and invasion of esophageal cancer cells dependent on a miR-203 inactivation. Finally, we identified miR-203 as a direct target of C/EBPβ LIP. Disruption of C/EBPβ LIP attenuated the EGF-mediated decrease in miR-203, whereas overexpression of C/EBPβ LIP alone markedly suppressed miR-203. In addition, we demonstrated that C/EBPβ LIP inhibited miR-203 transcription by directly interacting with a conserved distal regulatory element upstream of the miR-203 locus, and in doing so, orchestrated chromatin remodeling. In conclusion, our results have revealed a novel regulatory mechanism that involves C/EBPβ LIP-mediated down-regulation of miR-203, which plays a key role in EMT and metastasis.
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