Analysis of Polymorphism and Expression Profile of ASIC1 and IL-6 Genes in Patients with Gastric Cancer

Heydari-Mehrabadi, Abdulkuddous; Kordi-Tamandani, Dor Mohammad; Baranzehi, Tayebeh; Hemati, Simin

doi:10.31557/apjcp.2018.19.12.3451

Cited by 5 publications

(3 citation statements)

References 32 publications

(30 reference statements)

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“…IL-6 gene has been extensively studied in the development of GC, because inflammation and cancer are directly connected ( 13 , 23 ). Inflammatory processes, such as that caused by H. pylori infection, increase the synthesis of IL-6, activating the immune response and signaling pathways, which may contribute to the development of tumors.…”

Section: Discussionmentioning

confidence: 99%

“…In results that were consistent with ours, the expression of IL-6 was related to the promotion of human GC invasion and migration of AGS cells. Immunohistochemistry and in-situ hybridization have shown that IL-6 is highly expressed and is secreted from both gastric epithelial cells and inflammatory cells infiltrating the gastric mucosa in H. pylori infection ( 23 ). Zuo et al ( 27 ) obtained similar results, with greater expression in the cancer group than the control group.…”

Section: Discussionmentioning

confidence: 99%

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Increased expression of interleukin-6 gene in gastritis and gastric cancer

Santos

Pereira

Delabio

et al. 2021

Braz J Med Biol Res

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Helicobacter pylori (H. pylori) induces an intense inflammatory response, mediated by proinflammatory cytokines, including interleukin (IL)-6 and its membrane receptor (IL-6R), which activates important signaling pathways in the development of gastric disease and cancer. We investigated the gene and protein expression of IL-6 and IL-6R and the influence of polymorphisms rs1800795, rs1800796, and rs1800797 on its gene expression together with H. pylori infection. Furthermore, an in-silico analysis was performed to support our results. Gastric biopsies were obtained from patients with gastric symptoms and patients with gastric cancer (GC) and were divided into groups (Control, Gastritis, and Cancer). H. pylori was detected by PCR. Realtime-qPCR was employed to determine gene expression, and western blot assay was used to analyze protein expression levels. PCR-RFLP was used to characterize IL-6 polymorphisms. Bioinformatics analyses were performed using the Gene Expression Omnibus (GEO) database and GEO2R to screen out differentially expressed genes (DEGs). H. pylori was detected in 43.3% of the samples. Statistically significant differences were found for IL-6 (P=0.0001) and IL-6R (P=0.0005) genes among the three groups, regardless of the presence of H. pylori. Among patients with H. pylori infection, the IL-6 and IL-6R gene and protein expressions were significantly increased, highlighting IL-6 gene overexpression in patients with GC. No statistically significant differences were found for the rs1800795, rs1800796, and rs1800797 polymorphisms compared to IL-6 gene expression. The results indicated that the IL-6 polymorphisms do not influence its expression, but IL-6 and IL-6R expression seems to be altered by the presence of H. pylori.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased expression of interleukin-6 gene in gastritis and gastric cancer

Santos

Pereira

Delabio

et al. 2021

Braz J Med Biol Res

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“…Therefore, it was concluded that downregulation of ASIC1 inhibits the growth of GC by reducing autophagy [112]. Subsequent studies have shown that the expression of ASIC1 exhibits a significant correlation with an increased risk of GC as well as with GC cell migration and invasion [113,114]. Thus, hypoxia causes acidification of the extracellular environment, which in turn promotes the opening of the ASIC1 channel and ultimately regulates GC through autophagy.…”

Section: Hypoxia Promotes the Opening Of Asic1 Channels Which Regulate Gc Through Autophagymentioning

confidence: 99%

Alteration and dysfunction of ion channels/transporters in a hypoxic microenvironment results in the development and progression of gastric cancer

Chen

Zhang

et al. 2021

Cell Oncol.

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Background Gastric cancer (GC) is one of the most common malignant cancers in the world and has only few treatment options and, concomitantly, a poor prognosis. It is generally accepted now that the tumor microenvironment, particularly that under hypoxia, plays an important role in cancer development. Hypoxia can regulate the energy metabolism and malignancy of tumor cells by inducing or altering various important factors, such as oxidative stress, reactive oxygen species (ROS), hypoxia-inducible factors (HIFs), autophagy and acidosis. In addition, altered expression and/or dysfunction of ion channels/transporters (ICTs) have been encountered in a variety of human tumors, including GC, and to play an important role in the processes of tumor cell proliferation, migration, invasion and apoptosis. Increasing evidence indicates that ICTs are at least partly involved in interactions between cancer cells and their hypoxic microenvironment. Here, we provide an overview of the different ICTs that regulate or are regulated by hypoxia in GC. Conclusions and perspectives Hypoxia is one of the major obstacles to cancer therapy. Regulating cellular responses and factors under hypoxia can inhibit GC. Similarly, altering the expression or activity of ICTs, such as the application of ion channel inhibitors, can slow down the growth and/or migration of GC cells. Since targeting the hypoxic microenvironment and/or ICTs may be a promising strategy for the treatment of GC, more attention should be paid to the interplay between ICTs and the development and progression of GC in such a microenvironment.

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