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Background. Helicobacter pylori (Hp) infection is the strongest risk factor for gastric cancer (GC). However, the mechanisms of Hp-associated GC remain to be explored. Methods. The gene expression profiling (GSE111762) data were downloaded from the GEO database. Differentially expressed genes (DEGs) between normal samples (NO) and Hp-atrophic gastritis (GA) or Hp-GA and Hp-GC were identified by GEO2R. Gene Ontology and pathway enrichment analysis were performed using the DAVID database. lncRNA-TF-mRNA and ceRNA regulation networks were constructed using Cytoscape. The cross-networks were obtained by overlapping molecules of the above two networks. GSE27411 and GSE116312 datasets were employed for validation. Results. DEGs between NO and Hp-GA are linked to the activity of inward rectifying potassium channels, digestion, etc. DEGs between Hp-GA and Hp-GC were associated with digestion, positive regulation of cell proliferation, etc. According to the lncRNA-TF-mRNA network, 63 lncRNAs, 12 TFs, and 209 mRNAs were involved in Hp-GA while 16 lncRNAs, 11 TFs, and 92 mRNAs were contained in the Hp-GC network. In terms of the ceRNA network, 120 mRNAs, 18 miRNAs, and 27 lncRNAs were shown in Hp-GA while 72 mRNAs, 8 miRNAs, and 1 lncRNA were included in the Hp-GC network. In the cross-network, we found that immune regulation and differentiation regulation were important in the process of NO-GA. Neuroendocrine regulation was mainly related to the process of GA-GC. In the end, we verified that CDX2 plays an important role in the pathological process of NO to Hp-GA. Comparing Hp-GA with Hp-GC, DEGs (FPR1, TFF2, GAST, SST, FUT9, and SHH), TF, and GATA5 were of great significance. Conclusions. We identified the DEGs, and their lncRNA regulatory network of Hp-associated diseases might provide insights into the mechanism between Hp infection and GC. Furthermore, in-depth studies of the molecules might be useful to explore the multistep process of gastric diseases. [ABSTRACT FROM AUTHOR]

Background: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Methods: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. Results: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001). Conclusions: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs are endogenous small noncoding RNAs that aberrantly expressed in various carcinomas. MiR-148a and miR-152, which have the same "seed region", have not been comprehensively investigated in gastrointestinal cancers.Methods: Total RNA was extracted from the tissues of 101 patients with gastric cancer and 101 patients with colorectal cancer as well as their matched nontumor adjacent tissues. After polyadenylation and reverse transcription, the expression of miR-148a and miR-152 was determined using quantitative real-time polymerase chain reaction. The protein level of cholecystokinin B receptor, which might be the target gene of miR-148a and miR-152, was analyzed by Western blot in 40 patients with gastric cancer.Results: Expression levels of miR-148a and miR-152 in human gastric (p < 0.001 and p = 0.038, respectively, t-test) and colorectal (all p < 0.001) cancers were significantly lower than that in their matched nontumor adjacent tissues. Moreover, their low expression was also found in several gastrointestinal cancer cell lines compared with normal gastric epithelial cell line and normal colorectal tissue, respectively. A strong correlation was found between the expression of miR-148a and miR-152 (all p < 0.001, Pearson's correlation). Furthermore, low expression of miR-152 was correlated with increased tumor size (p = 0.023 and 0.004, respectively, Mann-Whitney U test) and advanced pT stage (p = 0.018 and 0.002, respectively) in gastrointestinal cancers. Low expression of miR-148a was also correlated with increased tumor size (p = 0.045 and 0.018, respectively) in gastrointestinal cancers, but only correlated with advanced pT stage (p = 0.023) in colorectal cancer. We also found the expression of miR-148a (p < 0.001, chi-square test) and miR-152 (p = 0.002) inversely correlated with cholecystokinin B receptor protein in gastric cancer.Conclusion: MiR-148a and miR-152 may be involved in the carcinogenesis of gastrointestinal cancers and might be potential biomarkers in these cancers. [ABSTRACT FROM AUTHOR]