Abstract
Our previous studies have suggested a protective role for H. pylori infection in the prognosis of gastric cancer. Based on those findings, we hypothesized that H. pylori-positive and -negative gastric cancers may exhibit different growth patterns and pathobiological behaviors, indicating different mechanisms of cancer progression. By microarray analysis, we studied miRNAs expression profiles in 42 gastric cancer patients, comparing 21 H. pylori-positive and 21 H. pylori-negative groups. Luciferase reporter assay and western blot were used to examine the potential target genes of the interested miRNA. In the present study, 53 miRNAs were significantly differentially expressed in H. pylori-positive and -negative gastric cancer tissues. We investigated the expression and function of one candidate, miR-143-3p, which was the most significantly increased miRNA in H. pylori-positive gastric cancer tissues. We observed that miR-143-3p expression was significantly decreased in gastric cancer tissues and cells, which correlated with late stage and lymph node metastasis. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-143-3p negatively regulated cell growth, apoptosis, migration and invasion. We further characterized AKT2 as a novel direct target of miR-143-3p. Knockdown of AKT2 expression mimicked the effects of miR-143-3p restoration. In conclusion, our data suggest that miR-143-3p acts as a novel tumor suppressive miRNA by regulating tumor growth, migration and invasion through directly targeting AKT2 gene. Further investigation is warranted to characterize the mechanisms underlying gastric cancer progression and may eventually contribute to its therapy.
Highlights
Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium that has been recognized as associated with gastric cancer by the World Health Organization [1]
We hypothesized that H. pylori-positive and -negative gastric cancers were quite different in growth patterns and pathobiological behavior, indicating different mechanisms of cancer progression
In the present study, updated survival data verified those findings. minas that were differentially expressed by H. pylori-positive and H. pylori-negative gastric cancers were identified using a microarray and were confirmed by Quantitative real-time PCR analysis (qRT-PCR)
Summary
Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium that has been recognized as associated with gastric cancer by the World Health Organization [1]. Mounting evidence has shown linkage between H. pylori infection and the development of gastric cancer. Studies have focused on the differences in survival of patients who are positive for H. pylori compared with those who are negative. Meimarakis et al identified H. pylori as an independent, beneficial prognostic factor in a prospective cohort [2]. Our previous study confirmed H. pylori status as a favorable prognostic factor in a Chinese prospective cohort [3]. We performed a meta-analysis to derive a more precise estimate of the association, which suggested a protective role for H. pylori infection in the prognosis of gastric cancer [4]. We hypothesized that H. pylori-positive and -negative gastric cancers were quite different in growth patterns and pathobiological behavior, indicating different mechanisms of cancer progression. Further knowledge of the two different types of gastric cancer may help to elucidate the identification of novel therapeutic targets
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