H. pylori infection alters repair of DNA double-strand breaks via SNHG17

Han, Tian; Jing, Xiaohui; Bao, Jiayu; Zhao, Lianmei; Zhang, Aidong; Miao, Renling; Guo, Hui; Zhou, Baojian; Zhang, Shang; Sun, Jiaren; Shi, Juan

doi:10.1172/jci125581

Cited by 56 publications

(44 citation statements)

References 64 publications

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“…H. pylori and the chronic inflammation that it induces enhance the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which cause DNA damage such as point mutations and double-strand DNA breaks, dysregulate signal transduction pathways, and induce apoptosis or autophagy of gastric epithelial cells ( Handa et al, 2010 ; Toller et al, 2011 ; Shimizu et al, 2017 ). The DNA repair system was found to be impaired in H. pylori -positive gastric epithelial cells ( Han et al, 2020 ). Thus, H. pylori may promote gastric carcinogenesis by causing genetic instability in host cells.…”

Section: Mechanisms Of Carcinogenesismentioning

confidence: 99%

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

et al. 2021

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The development of sequencing technology has expanded our knowledge of the human gastric microbiome, which is now known to play a critical role in the maintenance of homeostasis, while alterations in microbial community composition can promote the development of gastric diseases. Recently, carcinogenic effects of gastric microbiome have received increased attention. Gastric cancer (GC) is one of the most common malignancies worldwide with a high mortality rate. Helicobacter pylori is a well-recognized risk factor for GC. More than half of the global population is infected with H. pylori, which can modulate the acidity of the stomach to alter the gastric microbiome profile, leading to H. pylori-associated diseases. Moreover, there is increasing evidence that bacteria other than H. pylori and their metabolites also contribute to gastric carcinogenesis. Therefore, clarifying the contribution of the gastric microbiome to the development and progression of GC can lead to improvements in prevention, diagnosis, and treatment. In this review, we discuss the current state of knowledge regarding changes in the microbial composition of the stomach caused by H. pylori infection, the carcinogenic effects of H. pylori and non-H. pylori bacteria in GC, as well as the potential therapeutic role of gastric microbiome in H. pylori infection and GC.

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Section: Mechanisms Of Carcinogenesismentioning

confidence: 99%

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

et al. 2021

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“…In addition, overexpression of SNHG17 markedly altered the DNA repair system, which is essential for the maintenance of genomic stability. [19] According to the public database and our data, the present investigation revealed that expression levels of SNHG17 were markedly enhanced in RCC tissues and RCC cell lines. Speci cally, high SNHG17 expression levels were closely associated with advanced pathological features (tumor size, lymph node invasion, and distant organ metastasis) and the dismal survival of RCC patients.…”

Section: Discussionmentioning

confidence: 51%

LncRNA SNHG17 Promotes Tumor Progression and Predicts Poor Survival in Human Renal Cell Carcinoma via Sponging miR-328-3p

Dong

Liu

et al. 2020

Preprint

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Background: Accumulating data shows that dysregulation of long non-coding RNAs (lncRNAs) are involved in human tumors' occurrence and progression. Small nucleolar RNA host genes (SNHGs) are recently revealed to play a carcinogenic role in various human neoplasms. However, the functions and underlying mechanisms of lncRNA SNHG17 in renal cell carcinoma (RCC) are still elusive.Methods: We analyzed the relationship between SNHG17 expression levels and clinicopathologic characteristics and prognosis in patients with RCC according to TCGA RNA-sequencing data and our cohort data. Loss-of-function and gain-of-function experiments were conducted to examine the biological behaviors of SNHG17 on RCC cell proliferation, migration, invasion, apoptosis, and tumor growth in vivo. The interaction between SNHG17, miR-328-3p, and Histone’s H2A variant (H2AX) was verified by bioinformatics, dual-luciferase reporter gene, and RNA immunoprecipitation (RIP). Results: Highly expressed SNHG17 was evident in RCC tissue samples and cell lines, and SNHG17 overexpression was related to advanced TNM stage and reduced relapse-free and overall survival of patients with RCC. Knockdown of SNHG17 prohibited malignant phenotypes, whereas ectopic SNHG17 expression showed the opposite effects. More importantly, SNHG17 could upregulate the expression of H2AX by acting as a miR-328-3p sponge. In vivo experiments confirmed that SNHG17 promoted the growth of RCC tumors.Conclusion: SNHG17/miR-328-3p/H2AX axis might be involved in RCC progression, which provided a potential therapeutic target for RCC.

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“…Our results regarding the CagA-related decrease of RAD51 protein and RAD54L , during H. pylori infection, are consistent with Hanada et al [ 27 ]. In line with this, a recent report also suggested the CagA-related RAD51 decrease, documenting the deregulation of the SNHG17/miR-3909/RING1/RAD51 and SNHG17/NONO pathways, thereby attenuating HR and favoring the repair of DSBs via the error-prone NHEJ [ 121 ]. Decreased expression of POLD, RPA, RAD51, and RAD54L can result in diminished performance of HR, promotion of replication stress, and, therefore, increased DSB introduction [ 122 ].…”

Section: Discussionmentioning

confidence: 62%

Impact of Helicobacter pylori Infection and Its Major Virulence Factor CagA on DNA Damage Repair

et al. 2020

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Helicobacter pylori infection induces a plethora of DNA damages. Gastric epithelial cells, in order to maintain genomic integrity, require an integrous DNA damage repair (DDR) machinery, which, however, is reported to be modulated by the infection. CagA is a major H. pylori virulence factor, associated with increased risk for gastric carcinogenesis. Its pathogenic activity is partly regulated by phosphorylation on EPIYA motifs. Our aim was to identify effects of H. pylori infection and CagA on DDR, investigating the transcriptome of AGS cells, infected with wild-type, ΔCagA and EPIYA-phosphorylation-defective strains. Upon RNA-Seq-based transcriptomic analysis, we observed that a notable number of DDR genes were found deregulated during the infection, potentially resulting to base excision repair and mismatch repair compromise and an intricate deregulation of nucleotide excision repair, homologous recombination and non-homologous end-joining. Transcriptome observations were further investigated on the protein expression level, utilizing infections of AGS and GES-1 cells. We observed that CagA contributed to the downregulation of Nth Like DNA Glycosylase 1 (NTHL1), MutY DNA Glycosylase (MUTYH), Flap Structure-Specific Endonuclease 1 (FEN1), RAD51 Recombinase, DNA Polymerase Delta Catalytic Subunit (POLD1), and DNA Ligase 1 (LIG1) and, contrary to transcriptome results, Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1) upregulation. Our study accentuates the role of CagA as a significant contributor of H. pylori infection-mediated DDR modulation, potentially disrupting the balance between DNA damage and repair, thus favoring genomic instability and carcinogenesis.

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H. pylori infection alters repair of DNA double-strand breaks via SNHG17

Cited by 56 publications

References 64 publications

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

LncRNA SNHG17 Promotes Tumor Progression and Predicts Poor Survival in Human Renal Cell Carcinoma via Sponging miR-328-3p

Impact of Helicobacter pylori Infection and Its Major Virulence Factor CagA on DNA Damage Repair

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