| Grant number: | 13/03625-1 |
| Support Opportunities: | Scholarships in Brazil - Master |
| Start date: | June 01, 2013 |
| End date: | February 28, 2015 |
| Field of knowledge: | Biological Sciences - Genetics - Human and Medical Genetics |
| Principal Investigator: | Ana Elizabete Silva |
| Grantee: | Ana Flávia Teixeira Rossi Freire |
| Host Institution: | Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil |
Abstract Chronic inflammation provides a favorable microenvironment for neoplastic transformation, often due to persistent infection by pathogens. In this model, fits in gastric cancer as a result of infection by the bacterium Helicobacter pylori. Persistent infection by this bacterium promotes chronic inflammation, the main etiological factor for stomach cancer progression from atrophic gastritis, metaplasia and dysplasia. The bacterium also possesses virulence factors such as cagA and vacA and that modulate the host immune response, chronic inflammation and pathological changes of gastric mucosa. On the other hand, eradication of H. pylori may be able to reverse precancerous lesions by preventing malignant transformation, and the efficiency of time-dependent prevention of infection. Among the risk factors which contribute to host gastric carcinogenesis is the deregulation in expression of genes involved in the inflammatory response, such as altered expression of cytokines that can enhance or reduce the immune response caused by the pathogen. This change can be influenced by microRNAs (miRNAs) in the post-transcriptional level, and some studies have shown the importance of miRNAs in regulating inflammation as well as his deregulation resulting from infection by H. pylori. Moreover, some miRNAs can modulate cellular functions such as apoptosis, proliferation, differentiation and metabolism. Therefore, can act as oncogenes or tumor suppressor genes, influencing different types of cancers. There are still reports of action of miRNAs on the expression levels of mRNAs of interleukins in the gastric mucosa infected by H. pylori, but no studies regarding the relationship of both parameters in patients infected with H. pylori and subsequently underwent eradication therapy. Thus, the objectives of this study are: (a) evaluate the expression of microRNAs miR-103, miR200c, miR-223, miR-365, miR-370 and miR-375 in gastric biopsies of patients with dyspepsia H. pylori-positive before and after eradication therapy, compared with H. pylori-negative by real-time PCR; (b) Assess the mRNA quantitative expression of genes of the cytokines IL-1², IL-2, IL-6, IL12, TGFB-RII and TNF-± in the same samples and conditions for real-time PCR to investigate the occurrence and association between the expression of microRNAs and mRNA of cytokines, (c) evaluate the protein expression of cytokines with altered expression by immunohistochemistry and investigate possible association between expression of these proteins and microRNAs; (d) Investigate the association of genotypes CagA and VacA virulence of H. pylori with expression levels of miRNAs and cytokine genes. The results can reveal differences of these parameters before and after eradication treatment, and thus alter the host inflammatory response, but also show that the levels of cytokines and miRNAs are restored after elimination of the bacteria. Together these data may indicate some miRNA as biomarkers of inflammation and risk groups for progression to gastric cancer. (AU) | |
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