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Function of Non-coding RNA in Helicobacter pylori-Infected Gastric Cancer.

ABSTRACT: Gastric cancer is a common malignant tumor of the digestive system. Its occurrence and development are the result of a combination of genetic, environmental, and microbial factors. Helicobacter pylori infection is a chronic infection that is closely related to the occurrence of gastric tumorigenesis. Non-coding RNA has been demonstrated to play a very important role in the organism, exerting a prominent role in the carcinogenesis, proliferation, apoptosis, invasion, metastasis, and chemoresistance of tumor progression. H. pylori infection affects the expression of non-coding RNA at multiple levels such as genetic polymorphisms and signaling pathways, thereby promoting or inhibiting tumor progression or chemoresistance. This paper mainly introduces the relationship between H. pylori-infected gastric cancer and non-coding RNA, providing a new perspective for gastric cancer treatment.

SUBMITTER: Wang C

PROVIDER: S-EPMC8144459 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Function of Non-coding RNA in <i>Helicobacter pylori</i>-Infected Gastric Cancer.

Wang Chao C Hu Yiyang Y Yang Huan H Wang Sumin S Zhou Bo B Bao Yulu Y Huang Yu Y Luo Qiang Q Yang Chuan C Xie Xia X Yang Shiming S

Frontiers in molecular biosciences 20210511

Gastric cancer is a common malignant tumor of the digestive system. Its occurrence and development are the result of a combination of genetic, environmental, and microbial factors. <i>Helicobacter pylori</i> infection is a chronic infection that is closely related to the occurrence of gastric tumorigenesis. Non-coding RNA has been demonstrated to play a very important role in the organism, exerting a prominent role in the carcinogenesis, proliferation, apoptosis, invasion, metastasis, and chemor ...[more]

PMID: 34046430

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Project description:BackgroundHelicobacter pylori (H. pylori) is a type I biological carcinogen, which may cause about 75% of the total incidence of gastric cancer worldwide. H. pylori infection can induce and activate the cancer-promoting signaling pathway and affect the occurrence and outcome of gastric cancer through controlling the regulatory functions of long non-coding RNAs (lncRNAs). However, we have no understanding of the prognostic worth of lncRNAs for gastric cancer patients infected with H. pylori.MethodWe screened differentially expressed lncRNAs using DESeq2 method among TCGA database. And we built the H. pylori infection-related lncRNAs regulatory patterns. Then, we constructed H. pylori infection-based lncRNAs prognostic signatures for gastric cancer patients together with H. pylori infection, via uni-variable and multi-variable COX regression analyses. Based on receiver operator characteristic curve (ROC) analysis, we evaluated the prediction effectiveness for this model.ResultsWe identified 115 H. pylori infection-related genes were differentially expressed among H. pylori-infected gastric cancer tissues versus gastric cancer tissues. Functional enrichment analysis implies that H. pylori infection might interfere with the immune-related pathways among gastric cancer tissues. Then, we built H. pylori infection-related dys-regulated lncRNA regulatory networks. We also identified 13 differentially expressed lncRNAs were associated with prognosis for gastric cancer patients together with H. pylori infection. Kaplan-Meier analysis demonstrated that the lncRNA signatures were correlated with the poor prognosis. What is more, the AUC of the lncRNA signatures was 0.712. Also, this prognostic prediction model was superior to the traditional clinical characters.ConclusionWe successfully constructed a H. pylori-related lncRNA risk signature and nomogram associated with H. pylori-infected gastric cancer patients prognosis, and the signature and nomogram can predict the prognosis of these patients.

Project description:Helicobacter pylori (H. pylori) is well-known to be involved in gastric carcinogenesis, associated with deregulation of cell proliferation and epigenetic changes in cancer-related genes. H. pylori infection is largely acquired during childhood, persisting long-term in about half of infected individuals, a subset of whom will go on to develop peptic ulcer disease and eventually gastric cancer, however, the sequence of events leading to disease is not completely understood. Knowledge on carcinogenesis and gastric damage-related biomarkers is abundant in adult populations, but scarce in children. We performed an extensive literature review focusing on gastric cancer related biomarkers identified in adult populations, which have been detected in children infected with H. pylori. Biomarkers were related to expression levels (RNA or protein) and/or methylation levels (DNA) in gastric tissue or blood of infected children as compared to non-infected controls. In this review, we identified 37 biomarkers of which 24 are over expressed, three are under expressed, and ten genes are significantly hypermethylated in H. pylori-infected children compared to healthy controls in at least 1 study. Only four of these biomarkers (pepsinogen I, pepsinogen II, gastrin, and SLC5A8) have been studied in asymptomatically infected children. Importantly, 13 of these biomarkers (β-catenin, C-MYC, GATA-4, DAPK1, CXCL13, DC-SIGN, TIMP3, EGFR, GRIN2B, PIM2, SLC5A8, CDH1, and VCAM-1.) are consistently deregulated in infected children and in adults with gastric cancer. Future studies should be designed to determine the clinical significance of these changes in infection-associated biomarkers in children and their persistence over time. The effect of eradication therapy over these biomarkers in children if proven significant, could lead to modifications in treatment guidelines for younger populations, and eventually promote the development of preventive strategies, such as vaccination, in the near future.

Project description:BackgroundAlthough Helicobacter pylori (H.pylori) is the dominant gastrointestinal pathogen, the genetic and molecular mechanisms underlying H.pylori-related diseases have not been fully elucidated. Long non-coding RNAs (lncRNAs) have been identified in eukaryotic cells, many of which play important roles in regulating biological processes and pathogenesis. However, the expression changes of lncRNAs in human infected by H.pylori have been rarely reported. This study aimed to identify the dysregulated lncRNAs in human gastric epithelial cells and tissues infected with H.pylori.MethodsThe aberrant expression profiles of lncRNAs and mRNAs in GES-1 cells with or without H.pylori infection were explored by microarray analysis. LncRNA-mRNA co-expression network was constructed based on Pearson correlation analysis. Gene Ontology (GO) and KEGG Pathway analyses of aberrantly expressed mRNAs were performed to identify the related biological functions and pathologic pathways. The expression changes of target lncRNAs were validated by qRT-PCR to confirm the microarray data in both cells and clinical specimens.ResultsThree hundred three lncRNAs and 565 mRNAs were identified as aberrantly expressed transcripts (≥2 or ≤0.5-fold change, P < 0.05) in cells with H.pylori infection compared to controls. LncRNA-mRNA co-expression network showed the core lncRNAs/mRNAs which might play important roles in H.pylori-related pathogenesis. GO and KEGG analyses have indicated that the functions of aberrantly expressed mRNAs in H.pylori infection were related closely with inflammation and carcinogenesis. QRT-PCR data confirmed the expression pattern of 8 (n345630, XLOC_004787, n378726, LINC00473, XLOC_005517, LINC00152, XLOC_13370, and n408024) lncRNAs in infected cells. Additionally, four down-regulated (n345630, XLOC_004787, n378726, and LINC00473) lncRNAs were verified in H.pylori-positive gastric samples.ConclusionOur study provided a preliminary exploration of lncRNAs expression profiles in H.pylori-infected cells by microarray. These dysregulated lncRNAs might contribute to the pathological processes during H.pylori infection.

Dataset Information

Function of Non-coding RNA in Helicobacter pylori-Infected Gastric Cancer.

Publications

Function of Non-coding RNA in <i>Helicobacter pylori</i>-Infected Gastric Cancer.

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