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Minor allele of rs1057317 polymorphism in TLR4 is associated with increased risk of Helicobacter pylori ‐induced gastric cancer
Author(s) -
Wang YiWei,
Zhang CaiHong,
He Xiang
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27493
Subject(s) - genotype , helicobacter pylori , carcinogenesis , untranslated region , microbiology and biotechnology , allele , tlr4 , biology , odds ratio , gene , medicine , receptor , genetics , messenger rna
Background Helicobacter pylori (HP) plays a significant role in the carcinogenesis of gastric cancer (GC), the second leading cause of cancer‐related death worldwide. The aim of this study was to investigate the effect of rs1057317 polymorphism on the interaction between microRNA‐034a (miR‐034a) and toll‐like receptor 4 (TLR4), and their involvement in the HP‐associated GC. Methods Computation analyses, real‐time polymerase chain reaction, enzyme‐linked immunosorbent assay, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, and luciferase assays were performed to identify potential miRNAs involved in the carcinogenesis of HP‐induced GC. Subsequently, the effect of miR‐34a and recombinant TNFα‐interacting protein α (rTip‐α) on the expression of TLR4, interleukin (IL)‐6, and tumor necrosis factor α (TNF‐α) was measured. Results Three hundred and twelve HP‐positive GC patients (HP+ GC) and 380 HP‐negative GC patients (HP− GC) were enrolled into this study. It was found that, in HP‐positive patient, the AA genotype of the rs1057317 polymorphism was closely associated with the risk of GC (95% confidence interval, 1.12 to 2.70; odds ratio, 1.74; P = 0.0129). Furthermore, between the HP+ GC and HP− GC groups, miR‐34a was the only miRNA showing a significantly different expression. Subsequently, TLR4 was identified as a target gene of miR‐34a. Interestingly, miR‐34a evidently reduced the expression of TLR4 3′‐untranslated region (3′‐UTR) containing the C allele of the rs1057317 polymorphism, but the TLR4 3′‐UTR containing the A allele in the rs1057317 was not affected by miR‐34a. In addition, the expression of IL‐6 and TNF‐α was significantly downregulated by miR‐34a, but increased by rTip‐α. Both miR‐34a and rTip‐α could enhance the viability of cells, although the effect of rTip‐α was stronger. Conclusion The data of this study suggested that the rs1057317 polymorphism in the miR‐34a binding site of TLR4 may predict the risk of HP‐induced GC.