Project description:Transcriptomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout: Egln3, a negative regulator of NF-FB, was shown to be a direct miR-31 target; miR-31 inhibition/deletion resulted in suppression of miR-31-associated-EGLN3-NF-KB controlled inflammatory pathways.
Project description:To identify target genes of cancer-related microRNAs in human cancer, several cell lines (bladder cancer, prostate cancer, renal cell carcinoma, esophageal squamous cell carcinoma, and head and neck squamous cell carcinoma) were subjected to Agilent whole genome microarrays. Human cancer cell lines (BOY, T24, A498, 786-O, caki-1, LNCap, PC3, TE2, T.Tn, FaDu, SAS, HSC3, and IMC-3) were transfected with miRNAs (miR-375, miR-145, miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-138, miR-218, miR-874, miR-31, miR-222, miR-1285, and miR-206) or siRNAs (si-FOXA1_1, si-FOXA1_3, and si-TAGLN2). The miRNA-transfected human cancer cell lines were compared to control cell lines.
Project description:RATIONALE: Myocardial infarction (MI) triggers a dynamic microRNA response with the potential of yielding therapeutic targets. OBJECTIVE: We aimed to identify novel aberrantly expressed cardiac microRNAs post-MI with potential roles in adverse remodeling in a rat model, and to provide post-ischemic therapeutic inhibition of a candidate pathological microRNA in vivo. METHODS AND RESULTS: Following microRNA array profiling in rat hearts 2 and 14days post-MI, we identified a time-dependent up-regulation of miR-31 compared to sham-operated rats. A progressive increase of miR-31 (up to 91.4±11.3 fold) was detected in the infarcted myocardium by quantitative real-time PCR. Following target prediction analysis, reporter gene assays confirmed that miR-31 targets the 3´UTR of cardiac troponin-T (Tnnt2), E2F transcription factor 6 (E2f6), mineralocorticoid receptor (Nr3c2) and metalloproteinase inhibitor 4 (Timp4) mRNAs. In vitro, hypoxia and oxidative stress up-regulated miR-31 and suppressed target genes in cardiac cell cultures, whereas LNA-based oligonucleotide inhibition of miR-31 (miR-31i) reversed its repressive effect on target mRNAs. Therapeutic post-ischemic administration of miR-31i in rats silenced cardiac miR-31 and enhanced expression of target genes, while preserving cardiac structure and function at 2 and 4weeks post-MI. Left ventricular ejection fraction (EF) improved by 10% (from day 2 to 30 post-MI) in miR-31i-treated rats, whereas controls receiving scrambled LNA inhibitor or placebo incurred a 17% deterioration in EF. miR-31i decreased end-diastolic pressure and infarct size; attenuated interstitial fibrosis in the remote myocardium and enhanced cardiac output. CONCLUSION: miR-31 induction after MI is deleterious to cardiac function while its therapeutic inhibition in vivo ameliorates cardiac dysfunction and prevents the development of post-ischemic adverse remodeling.
Project description:We report that miR-31 injection Reverses Overexpression of the Proinflammatory genes in Esophageal Preneoplasia in the Zinc Deficient Rat
Project description:miR-223 is step-wise increasingly up-regulated in the normal esophagus - Barrett's esophagus -esophageal adenocarcinoma carcinoma sequence. In this study, we aimed to determine the function of miR-223 in esophageal adenocarcinoma carcinogenesis.
Project description:Identifying biomarkers predictive for early esophageal cancer detection is critical considering the dismal survival rates. We investigated the involvement of microRNAs (miRNAs), their utility as biomarkers, and their association with survival in esophageal cancer, including Barrett’s associated and sporadic adenocarcinoma (ADC), and squamous cell carcinoma (SCC). MiRNA expression was measured in cancerous and adjacent non-cancerous tissue pairs collected from 76 US and Japanese patients enrolled in 3 distinct cohorts. In ADC patients, miR-21, miR-194, miR-293, and miR-223 expression was elevated, while miR-375 and miR-203 expression was reduced in cancerous tissue compared to non-cancerous tissue. Increased levels of miR-192 and miR-194 were observed in Barrett’s associated compared to sporadic ADC cancerous tissue. In SCC patients, miR-21, miR-181b, miR-155, and miR-146b expression was elevated while miR-375 and miR-203 levels were reduced in cancerous tissue compared to non-cancerous tissue. Significantly, elevated mir-21 expression in non-cancerous tissue was strongly associated with worse prognosis, independent of nodal status and age. Sample classification using miRNA expression yielded accuracies as high as 86% for diagnosis and 78% for Barrett’s esophagus status. Our results highlight that miRNAs are deregulated in esophageal carcinogenesis and Barrett’s esophagus, and that their expression is associated with survival in cancer patients. Sample classification using miRNA expression demonstrates their potential utility as biomarkers for esophageal carcinoma diagnosis.
Project description:The purposes of this study were to compare and analyze the expression differences of papillary thyroid carcinoma (PTC) induced by BrafV600E after knockdown of miR-31 deletion. And in order to gain insights into global gene expression regulated by miR-31 in human PTC cells, RNA-Seq experiments were performed in K1 cells with knockdout of miR-31.
Project description:To further understand different gene expression of miR-31 knockout mouse colon and normal colon, we have employed colonic epithelium microarray expression profiling as a discovery platform to identify different genes with miR-31 knockout mouse colon and normal colon.comparision with normal colonic epithelium,upgene is 285 and downgene is 178 in knockout group.
Project description:We have investigated expressed microRNA in cryo-preserved esophageal cancer tissues using advanced microRNA microarray techniques. Our microarray analyses reveal a unique microRNA expression signature composed of 40 genes which can distinguish normal from malignant esophageal tissue. Some microRNAs could be correlated with the different clinico-pathological classifications. For example, high hsa-miR-103, -107, -23b expression correlated with poor overall disease-free survival of esophageal cancer patients. These results indicate that microRNA expression profiles are important diagnostic and prognostic markers of esophageal cancer, which might be analyzed simply using economical approaches such as RT-PCR. Keywords: microRNA, esophageal squamous cell carcinoma