Abstract
BackgroundGastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. However, miR-584 expression pattern in gastric cancer development has remained unclear. This study aims to analyze the expression of miR-584 in gastric cancer samples and investigates the associations between this miRNA and H. pylori infection and clinical characteristics.MethodsThe expression level of miR-584 was studied in primary gastric cancers versus healthy control gastric mucosa samples using the RT-qPCR method. The clinical data were analyzed statistically in terms of miR-584 expression. In silico studies were employed to study miR-584 more broadly in order to assess its expression and find new potential target genes.ResultsBoth experimental and in silico studies showed up-regulation of miR-584 in patients with gastric cancer. This up-regulation seems to be induced by H. pylori infection since the infected samples showed increased levels of miR-584 expression. Deeper analyses revealed that miR-584 undergoes a dramatic down-regulation in late stages, invasive and lymph node-metastatic gastric tumors. Bioinformatics studies demonstrated that miR-584 has a substantial role in cancer pathways and has the potential to target STAT1 transcripts. Consistent with the inverse correlation between TCGA RNA-seq data of miR-584 and STAT1 transcripts, the qPCR analysis showed a significant negative correlation between these two RNAs in a set of clinical samples.ConclusionmiR-584 undergoes up-regulation in the stage of primary tumor formation; however, becomes down-regulated upon the progression of gastric cancer. These findings suggest the potential of miR-584 as a diagnostic or prognostic biomarker in gastric cancer.
Highlights
Gastric cancer is the fifth most common cancer worldwide
Results miR-584 is highly expressed in tumor samples The expression level of miR-584 was determined by RTqPCR, followed by the statistical analysis in four groups, including patients with H. pylori infection (n = 14), patients without H. pylori infection (n = 12), control samples infected by H. pylori (n = 6) and non-infected control samples (n = 5)
The in silico data strongly demonstrate the overexpression of miR-584 overexpression in gastric cancer samples, which has been validated in our study on the clinical specimens
Summary
Gastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. H. pylori infection is one of the noticeable correlated factors with gastric neoplasm through modulating inflammatory signaling pathways in the mucosa of the stomach. This infection can promote the risk of gastric cancer more than six-fold [4, 5]. MiRNAs are an emerging class of non-coding RNAs containing less than 24 nucleotides, which bind mainly to the 3′-UTR of their target mRNAs. Genetically, microRNAs (miRNAs) are important molecules that are deregulated in gastric cancer [6,7,8,9]. H. pylori infection is one of the vital factors responsible for miRNA dysregulation through regulating the inflammatory mediators [14,15,16,17]. miR-21 [18, 19], miR-25 [19], miR-93 [20], miR-146a [21], miR-155 [22], miR-196 [23], miR-200b/c [15, 24], miR-222 [25], miR-223 [20], miR-584 and miR1290 [26] are the well-known H. pylori-induced upregulated miRNAs, while let-7b [24, 27], miR-103 [24], miR-370 [28], miR-371, miR-372, miR-373 [29], miR375 [24] and miR-449 [30] are the down-regulated ones
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