In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2412-2412
Abstract:
The bacterial pathogen H. pylori chronically infects the human gastric mucosa and is the leading risk factor for the development of gastric cancer. It is believed that during the infection the organism causes an impairment of DNA repair in the gastric epithelium. Thus, we evaluated the in vitro modulatory effects of H. pylori infection in the DNA mismatch repair (MMR). To evaluate the effects of H. pylori on MMR, AGS gastric carcinoma cell line and the H. pylori strain P12 were used in co-culture experiments for 4, 8 and 12 h. In addition, to analyze the potential effects of virulence factors on MMR, the ΔcagPAI, ΔvacA, ΔbabA, ΔhopQ, and Δtfs4 mutants were also subjected to co-culture experiments. The expression levels of EXO1, MLH1, MSH2, MSH3, MSH6, POLD3, PMS1, and PMS2 were assessed by real-time PCR. Moreover, expression levels of five previously screened miRNAs (miR-142-5p, miR-150-5p, miR-155-5p, miR-3163, and miR-4775), which are predicted to target MMR genes, were also evaluated by real-time PCR. Our data show that H. pylori infection significantly down-regulates the expression of all selected genes. Regarding the virulence factors, the results suggest that the modulation on gene expression might be dependent on cagPAI, vacA, and the type IV secretion (TFS4) system. Although the infection up-regulates miR-150-5p, miR-155-5p, miR-3163, and miR-4775, only the expression of miR-155-5p is related with virulence factors. Briefly, this study shows that H. pylori regulates the expression of several MMR genes, and it may be related with cagPAI, vacA, and the TFS4 system. Taking into account that MLH1, MSH2, and MSH6 are the miR-155-5p predicted targets, these preliminary data suggest that the observed virulence factor-dependent repression of miR expression could be responsible for the down-regulation of these MMR genes. Citation Format: Juliana C. Santos, Victor R. de Almeida, Wolfgang Fischer, Rainer Haas, Marcelo L. Ribeiro. The modulatory effects of H. pylori infection in the DNA mismatch repair. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2412. doi:10.1158/1538-7445.AM2014-2412
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-2412
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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