hsa-miR-29c and hsa-miR-135b differential expression aspotential biomarker of gastric carcinogenesis

查看全文 作　　者：Amanda Ferreira [1,2]Vidal;Aline MP [1,2]Cruz;Leandro [1,2]Magalhães;Adenilson L [1,2]Pereira;Ana KM [1,2]Anaissi;Nélisson CF [3,4]Alves;Paulo JBS [5]Albuquerque;Rommel MR [4,6]Burbano;Samia [6,7]Demachki;Ândrea Ribeiro-dos-[2,6]Santos

机构地区：[1]Pós-Graduação em Genética e Biologia Molecular,Universidade Federal do Pará,Cidade Universitária Prof.JoséSilveira Netto,Belém,PA 66075-970,Brasil;[2]Laboratório de Genética Humana e Médica,Instituto de Ciências Biológicas,Universidade Federal do Pará,Belém,PA 66075-970,Brasil;[3]Pós-Graduação em Neurociências e Biologia Molecular,Universidade Federal do Pará,Belém,PA 66075-970,Brasil;[4]Laboratório de Citogenética Humana-Instituto de Ciências Biológicas,Universidade Federal do Pará,Belém,PA 66075-970,Brasil;[5]Hospital São Camilo e São Luís-Rua Dr.Marcelo Cândia,Macapá,AP 68901-901,Brasil;[6]Hospital Universitário João de Barros Barreto,Universidade Federal do Pará,Belém,PA 66075-970,Brasil;[7]Instituto de Ciências da Saúde,Universidade Federal do Pará,Belém,PA 66075-970,Brasil

出　　处：《World Journal of Gastroenterology》索引2016年第22卷第6期,共11页

基　　金：Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico;Fundacao Amazonia Paraense de Amparo a Pesquisa;Coordenacao de Aperfeicoamento de Pessoal de Nível Superior/Bio Computacional,No.3381/2013 摘　　要：AIM: To investigate the expression profiles of hsa-mi R-29 c and hsa-mi R-135 b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-mi R-29 c and hsa-mi R-135 b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinaltype gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-mi R-29 c and hsa-mi R-135 b expression profiles in the grouped samples was evaluated by ANOVA and Student's t-test tests. The results were adjusted for multiple testing by using Bonferroni's correction. P values ≤ 0.05 were considered statistically significant. To evaluate hsa-mi R-29 c and hsa-mi R-135 b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-mi R-29 c and hsa-mi R-135 b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis.RESULTS: The expression levels of hsa-mi R-29 c were higher in normal gastric mucosal samples, and decreased progressively in non-atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal-type gastric adenocarcinoma samples. The expression of hsa-mi R-29 c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This micro RNA(mi RNA) has a good discriminatory accuracy between normal gastric samples and(1) intestinal-type gastric adenocarcinoma; and(2) intestinal metaplasia, and regulates the DMNT3 A oncogene. hsa-mi R-135 b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples and down-regulated in normal gastric mucosa and intestinal-type gastric adenocarcinoma samples. Non-atrophic chronic gastritis and intestinal metaplasia are significantly different from normal gastric mucosa samples. hsa-mi R-135 b expression presented a greater discriminatory accuracy between normal samples and gastric lesions. This mi RNA was associated with Helicobacter pylori presence in non-atrophic chronic gastritis samples and regulates the APC and KLF4 tumour suppressor genes.CONCLUSION: Our results provide evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-mi R-29 c and hsa-mi R-135 b are promising biomarkers of gastric carcinogenesis. 关键词：Gastric cancer Gastric lesions Micro RNA BIOMARKER CARCINOGENESIS

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hsa-miR-29c and hsa-miR-135b differential expression aspotential biomarker of gastric carcinogenesis

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