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Kuang W, Xu J, Xu F, Huang W, Majid M, Shi H, Yuan X, Ruan Y, Hu X. Current study of pathogenetic mechanisms and therapeutics of chronic atrophic gastritis: a comprehensive review. Front Cell Dev Biol 2024; 12:1513426. [PMID: 39720008 PMCID: PMC11666564 DOI: 10.3389/fcell.2024.1513426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 11/25/2024] [Indexed: 12/26/2024] Open
Abstract
Chronic atrophic gastritis (CAG) is a prevalent digestive system disease characterized by atrophy of the gastric mucosa and the disappearance of inherent gastric glands. According to the theory of Correa's cascade, CAG is an important pathological stage in the transformation from normal condition to gastric carcinoma. In recent years, the global incidence of CAG has been increasing due to pathogenic factors, including Helicobacter pylori infection, bile reflux, and the consumption of processed meats. In this review, we comprehensively described the etiology and clinical diagnosis of CAG. We focused on elucidating the regulatory mechanisms and promising therapeutic targets in CAG, with the expectation of providing insights and theoretical support for future research on CAG.
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Affiliation(s)
- Weihong Kuang
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
| | - Jialin Xu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Fenting Xu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Weizhen Huang
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Muhammad Majid
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Hui Shi
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
| | - Xia Yuan
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Yongdui Ruan
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Cancer Center, The First Huizhou Affiliated Hospital, Guangdong Medical University, Huizhou, China
| | - Xianjing Hu
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Traditional Chinese Medicines for Prevention and Treatment of Digestive Diseases, Guangdong Medical University, Dongguan, China
- Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
- Department of Acupuncture, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
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Wang C, Li W, Shao L, Zhou A, Zhao M, Li P, Zhang Z, Wu J. Both extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles are involved in gastric/extragastric diseases. Eur J Med Res 2023; 28:484. [PMID: 37932800 PMCID: PMC10626716 DOI: 10.1186/s40001-023-01458-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 10/18/2023] [Indexed: 11/08/2023] Open
Abstract
Bacterial-derived extracellular vesicles (EVs) have emerged as crucial mediators in the cross-talk between hosts and pathogens, playing a significant role in infectious diseases and cancers. Among these pathogens, Helicobacter pylori (H. pylori) is a particularly important bacterium implicated in various gastrointestinal disorders, gastric cancers, and systemic illnesses. H. pylori achieves these effects by stimulating host cells to secrete EVs and generating internal outer membrane vesicles (OMVs). The EVs derived from H. pylori-infected host cells modulate inflammatory signaling pathways, thereby affecting cell proliferation, apoptosis, cytokine release, immune cell modification, and endothelial dysfunction, as well as disrupting cellular junctional structures and inducing cytoskeletal reorganization. In addition, OMVs isolated from H. pylori play a pivotal role in shaping subsequent immunopathological responses. These vesicles incite both inflammatory and immunosuppressive reactions within the host environment, facilitating pathogen evasion of host defenses and invasion of host cells. Despite this growing understanding, research involving H. pylori-derived EVs remains in its early stages across different domains. In this comprehensive review, we present recent advancements elucidating the contributions of EV components, such as non-coding RNAs (ncRNAs) and proteins, to the pathogenesis of gastric and extragastric diseases. Furthermore, we highlight their potential utility as biomarkers, therapeutic targets, and vehicles for targeted delivery.
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Affiliation(s)
- Chengyao Wang
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Wenkun Li
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Linlin Shao
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Anni Zhou
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Mengran Zhao
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Peng Li
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Zheng Zhang
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
| | - Jing Wu
- Department of Gastroenterology National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, BeijingKey Laboratory for Precancerous Lesion of Digestive Disease, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
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Bhattacharya A. Epigenetic modifications and regulations in gastrointestinal diseases. EPIGENETICS IN ORGAN SPECIFIC DISORDERS 2023:497-543. [DOI: 10.1016/b978-0-12-823931-5.00005-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Zhang ML, Fan YX, Meng R, Cai WK, Yin SJ, Zhou T, Huang YH, Wang P, Jiang FF, Yang M, He GH. Proton Pump Inhibitors and Cancer Risk: An Umbrella Review and Meta-analysis of Observational Studies. Am J Clin Oncol 2022; 45:475-485. [PMID: 36255347 DOI: 10.1097/coc.0000000000000949] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Increasing evidence suggested that proton pump inhibitors (PPIs) use might affect the development of cancers, but previous conclusions remain controversial. Therefore, an umbrella review was performed to clarify the associations between PPIs and various types of cancer by summarizing the existing meta-analyses and systematic reviews. METHODS We searched PubMed, Cochrane Library, Embase, CNKI, Wanfang, and VIP database up to June 2022 for eligible meta-analyses or systematic reviews. The summary effect size, 95% CI, heterogeneity, small study effect, and 95% prediction interval were considered in the present study. A Measurement Tool to Assess Systematic Review 2 and grading of recommendation, assessment, development, and evaluation were used to assess methodological quality and evidence. RESULTS The umbrella review included 21 meta-analyses containing 65 studies and 10 cancer types with 6.8 million subjects. The results showed that PPI use was significantly associated with increased risks of certain types of cancer, including gastric cancer (odds ratio [OR]: 2.07; 95% CI, 1.30 to 3.29), pancreatic cancer (OR: 1.73; 95% CI, 1.23 to 2.44), colorectal cancer (OR: 1.84; 95% CI, 1.26 to 2.67), and liver cancer (OR: 1.80; 95% CI, 1.27 to 2.54), but was not associated with esophageal cancer. In addition, PPI use was associated with decreased risk of breast cancer (OR: 0.69; 95% CI, 0.50 to 0.96). CONCLUSIONS These findings suggested that clinicians should pay more attention to the occurrence of gastric cancer, pancreatic cancer, colorectal cancer, and liver cancer in patients who used PPIs, and PPI prescription should be written only when an accurate specific diagnosis has been made. Furthermore, additional PPIs to the treatment regimen may be benefit for women with a higher-than-average risk of breast cancer.
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Affiliation(s)
- Man-Li Zhang
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
- Kunming Medical University, Kunming, China
| | - Yu-Xin Fan
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
| | - Rui Meng
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
- Kunming Medical University, Kunming, China
| | - Wen-Ke Cai
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
| | - Sun-Jun Yin
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
| | - Tao Zhou
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
| | - Yan-Hua Huang
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
| | - Ping Wang
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
| | - Fang-Fang Jiang
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
| | - Mei Yang
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
- Kunming Medical University, Kunming, China
| | - Gong-Hao He
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army
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Liu Q, Tang J, Chen S, Hu S, Shen C, Xiang J, Chen N, Wang J, Ma X, Zhang Y, Zeng J. Berberine for gastric cancer prevention and treatment: Multi-step actions on the Correa's cascade underlie its therapeutic effects. Pharmacol Res 2022; 184:106440. [PMID: 36108874 DOI: 10.1016/j.phrs.2022.106440] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/30/2022] [Accepted: 09/07/2022] [Indexed: 11/09/2022]
Abstract
Gastric carcinoma (GC) is a complex multifactorial disease occurring as sequential events commonly referred to as the Correa's cascade, a stepwise progression from non-active or chronic active gastritis, to gastric precancerous lesions, and finally, adenocarcinoma. Therefore, the identification of novel agents with multi-step actions on the Correa's cascade and those functioning as multiple phenotypic regulators are the future direction for drug discovery. Recently, berberine (BBR) has gained traction owing to its pharmacological properties, including anti-inflammatory, anti-cancer, anti-ulcer, antibacterial, and immunopotentiation activities. In this article, we investigated and summarized the multi-step actions of BBR on Correa's cascade and its underlying regulatory mechanism in gastric carcinogenesis for the first time, along with a discussion on the strength of BBR to prevent and treat GC. BBR was found to suppress H. pylori infection, control mucosal inflammation, and promote ulcer healing. In the gastric precancerous lesion phase, BBR could reverse mucosal atrophy and prevent lesions in intestinal metaplasia and dysplasia by regulating inflammatory cytokines, promoting cell apoptosis, regulating macrophage polarization, and regulating autophagy. Additionally, the therapeutic action of BBR on GC was partly realized through the inhibition of cell proliferation, migration, and angiogenesis; induction of apoptosis and autophagy, and enhancement of chemotherapeutic drug sensitivity. BBR exerted multi-step actions on the Correa's cascade, thereby halting and even reversing gastric carcinogenesis in some cases. Thus, BBR could be used to prevent and treat GC. In conclusion, the therapeutic strategy underlying BBR's multi-step action in the trilogy of Correa's cascade may include "prevention of gastric mucosal inflammation (Phase 1); reversal of gastric precancerous lesions (Phase 2), and rescue of GC (Phase 3)". The NF-κB, PI3K/Akt, and MAPK signaling pathways may be the key signaling transduction pathways underlying the treatment of gastric carcinogenesis using BBR. The advantage of BBR over conventional drugs is its multifaceted and long-term effects. This review is expected to provide preclinical evidence for using BBR to prevent gastric carcinogenesis and treat gastric cancer.
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Affiliation(s)
- Qingsong Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China
| | - Jianyuan Tang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China
| | - Shuanglan Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China
| | - Shuangyuan Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China
| | - Caifei Shen
- Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China
| | - Juyi Xiang
- Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China
| | - Nianzhi Chen
- State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, 400016 Chongqing, China
| | - Jundong Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, 611137 Chengdu, China.
| | - Yi Zhang
- Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China.
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 610072 Chengdu, China.
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Prediction of Blood miRNA-mRNA Regulatory Network in Gastric Cancer. Rep Biochem Mol Biol 2021; 10:243-256. [PMID: 34604414 DOI: 10.52547/rbmb.10.2.243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 10/13/2020] [Indexed: 01/15/2023]
Abstract
Background The aim of the study was to suggest a high specific and sensitive blood biomarker for early GC diagnosis. Methods the expression data of miRNAs and mRNAs were collected from the blood samples of the GC patients based on literature mining. Bioinformatics tools and databases (PANTHER, TargetScan, miRTarBase, miRDB, STRING, and Cytoscape) were used to predict the regulatory relationship. Subsequently, expression level of the selected miRNA was evaluated in the blood samples of gastritis patients to recognize the common miRNA between the GC and gastritis patients. Results Analysis of 40 target genes by MCODE (installed in Cytoscape software) indicated 4 hub genes (WWP1, SKP2, KLHL42, and FBXO11) as a significant cluster in the PPI network related to miR-21, with Node Score Cutoff: 0.2, Degree Cutoff: 2 and K-Core: 2. In addition, the miRNA RT-qPCR results showed that, the expression level of miR-21 was significantly higher in gastritis group compared to the healthy group (p< 0.05). Conclusion the present study clearly demonstrated the increasing level of blood miR-21 among the gastritis patients infected by H. pylori. Therefore, the altered miRNAs, especially overexpression of onco-miRs, may identify a potential link between miRNAs and pathogenesis of the H. pylori-related complications.
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Dos Santos MP, Pereira JN, De Labio RW, Carneiro LC, Pontes JC, Barbosa MS, Smith MDAC, Payão SLM, Rasmussen LT. Decrease of miR-125a-5p in Gastritis and Gastric Cancer and Its Possible Association with H. pylori. J Gastrointest Cancer 2021; 52:569-574. [PMID: 32504357 DOI: 10.1007/s12029-020-00432-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of this study was to evaluate the expression of miR-125a-5p in patients with dyspeptic symptoms and gastric cancer, correlating them with the development of this cancer and H. pylori. METHODS Patients were divided in groups according to histopathological analysis (control, gastritis, and cancer groups). Polymerase chain reaction was performed to detect H. pylori and real-time quantitative PCR to determine miR-125a-5p expression. RESULTS H. pylori was detected in 44% of the patients, with prevalence in the gastritis and cancer groups. A statistically significant decrease of miR-125a-5p expression was found in the control positive (p = 0.0183*), gastritis positive (p = 0.0380*), and cancer positive (p = 0.0288*) groups when compared with the control negative group. CONCLUSION We suggest that decreased expression of the miRNA-125a-5p associated with the presence of the H. pylori is an important mechanism in gastric diseases and could be a possible marker for early diagnosis of gastric cancer.
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Affiliation(s)
- Mônica Pezenatto Dos Santos
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Jéssica Nunes Pereira
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Roger Willian De Labio
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Lilian Carla Carneiro
- Institute of Tropical Pathology and Public Health, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil
| | - Jaqueline Correia Pontes
- Institute of Tropical Pathology and Public Health, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil
| | - Mônica Santiago Barbosa
- Institute of Tropical Pathology and Public Health, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil
| | | | - Spencer Luíz Marques Payão
- Genetics Laboratory, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil
| | - Lucas Trevizani Rasmussen
- Biochemistry Department, Marília Medical School (FAMEMA), Lourival Freire, 240, Bairro Fragata, Marília, São Paulo, CEP 17519-050, Brazil.
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Khayam N, Nejad HR, Ashrafi F, Abolhassani M. Expression Profile of miRNA-17-3p and miRNA-17-5p Genes in Gastric Cancer Patients with Helicobacter pylori Infection. J Gastrointest Cancer 2021; 52:130-137. [PMID: 31997281 DOI: 10.1007/s12029-019-00319-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The most common chronic bacterial infection is Helicobacter pylori. The connection between chronic H. pylori infection and gastric cancer is recognized. The early detection of gastric cancer improves survival. miRNAs regulate gene expression in eukaryotes by inhibiting mRNA translocation or degradation. The objective of this study was to compare the expression of miRNA-17-3p and miRNA-17-5p genes in gastric cancer patients with Helicobacter pylori infection. METHODS Herein, 30 isolates were identified as H. pylori based on urease test, and 30 and 12 cases were isolated from gastric cancer patients and non-Helicobacter pylori cases as control, respectively. A peripheral blood sample was collected from patients. Analysis of total mRNA extracts from peripheral blood samples, for gene expression changes (miRNA-17-3p and miRNA-17-5p) by quantitative real-time polymerase chain reaction (qRT-PCR), was done. RESULTS As said by the results, p values showed that expression levels of miRNA-17-3p and miRNA-17-5p were significantly higher in H. pylori-positive GC patients and H. pylori-positive non-GC patients with comparing by healthy controls. So, there was no significant difference between expression levels of miRNA-17-3p and miRNA-17-5p in H. pylori-positive GC patients and H. pylori-positive non-GC patients. CONCLUSION Considering our results, the high expression of miRNA-17-3p and miRNA-17-5p has a direct relationship with increased cell proliferation, inhibition of tumor cell apoptosis and tumor angiogenesis, in addition to miRNAs play an important role as biomarkers in helping for detection of the patient by H. pylori infection to become cancerous. Therefore, it can be used to make specific diagnostic kits and to treat patients.
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Affiliation(s)
- Nazanin Khayam
- Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Hamideh Rouhani Nejad
- Department of Microbiology, Islamic Azad University, North Tehran Branch, Tehran, Iran.
| | - Fatemeh Ashrafi
- Department of Microbiology, Islamic Azad University, North Tehran Branch, Tehran, Iran
| | - Mohsen Abolhassani
- Hybridoma Lab., Dept. of Immunology, Pasteur Institute of Iran, Tehran, 13164, Iran
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Inokuchi K, Ochiya T, Matsuzaki J. Extracellular miRNAs for the Management of Barrett's Esophagus and Esophageal Adenocarcinoma: A Systematic Review. J Clin Med 2020; 10:E117. [PMID: 33396321 PMCID: PMC7795564 DOI: 10.3390/jcm10010117] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 12/26/2020] [Accepted: 12/28/2020] [Indexed: 02/06/2023] Open
Abstract
Esophageal adenocarcinoma (EAC), the major histologic type of esophageal cancer (EC) in Western countries, is a disease with a poor prognosis, primarily due to usual diagnosis at an advanced stage. The prevalence of EAC has increased in recent years, both in Western countries and in Asia. Barrett's esophagus (BE) is a precursor lesion of EAC. Therefore, early detection and proper management of BE and EAC is important to improve prognosis. Here, we systematically summarize current knowledge about the potential utility of extracellular microRNAs (miRNAs), which are thought to be non-invasive biomarkers for many diseases, for these purposes. A search of the PubMed and Embase databases identified 22 papers about extracellular miRNAs that have potential utility for management of EAC. Among them, 19 were EAC-related and ten were BE-related; some of these dealt with both conditions. The articles included studies reporting diagnosis, prognosis, and treatment responses. Multiple papers report dysregulation of miR-194-5p in BE and miR-21-5p, -25-3p, and -93-5p in EAC. Although it will take time to utilize these miRNAs in clinical practice, they are likely to be useful non-invasive markers in the future.
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Affiliation(s)
- Kazumi Inokuchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;
| | - Takahiro Ochiya
- Department of Molecular and Cellular Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan;
| | - Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;
- Department of Molecular and Cellular Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan;
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Kim N. Reversal of the Methylation-Associated Regulation of miR-200a/b by Helicobacter pylori Eradication Contributes to the Chemoprevention of Gastric Carcinogenesis. Gut Liver 2020; 14:533-534. [PMID: 32921637 PMCID: PMC7492488 DOI: 10.5009/gnl20251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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11
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Baz M, Ibrahim T. Role of microRNAs in the predisposition to gastrointestinal malignancies. World J Clin Cases 2020; 8:1580-1585. [PMID: 32420299 PMCID: PMC7211524 DOI: 10.12998/wjcc.v8.i9.1580] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 03/26/2020] [Accepted: 04/24/2020] [Indexed: 02/05/2023] Open
Abstract
MicroRNAs (miRNAs) are highly deregulated in cancer and play a role in the initiation of tumorigenesis. Recently, miRNAs have attracted attention in gastrointestinal (GI) cancers. Single nucleotide polymorphisms (SNPs) could affect the genes involved in each step of miRNA biosynthesis. Several meta-analyses of case-control studies have assessed the association between miRNA “pathway” gene-SNPs (including biosynthesis regulators and binding sites) and susceptibility to GI cancers. We present in this mini-review the current knowledge on the association between miRNAs “pathway” genes and GI cancer predisposition. The interaction between miRNA/regulators/binding site-SNPs and environmental as well as genomic factors is an interesting field that should be exploited in future studies.
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Affiliation(s)
- Maria Baz
- Department of Tumor Molecular Biology, Gustave Roussy Cancer Campus, Villfejuif 94805, France
| | - Tony Ibrahim
- Department of Medical Oncology, Gustave Roussy Cancer Campus, Villfejuif 94805, France
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12
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Qian S, Golubnitschaja O, Zhan X. Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles. EPMA J 2019; 10:365-381. [PMID: 31832112 PMCID: PMC6882964 DOI: 10.1007/s13167-019-00194-x] [Citation(s) in RCA: 131] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 11/06/2019] [Indexed: 12/24/2022]
Abstract
A strong relationship exists between tumor and inflammation, which is the hot point in cancer research. Inflammation can promote the occurrence and development of cancer by promoting blood vessel growth, cancer cell proliferation, and tumor invasiveness, negatively regulating immune response, and changing the efficacy of certain anti-tumor drugs. It has been demonstrated that there are a large number of inflammatory factors and inflammatory cells in the tumor microenvironment, and tumor-promoting immunity and anti-tumor immunity exist simultaneously in the tumor microenvironment. The typical relationship between chronic inflammation and tumor has been presented by the relationships between Helicobacter pylori, chronic gastritis, and gastric cancer; between smoking, development of chronic pneumonia, and lung cancer; and between hepatitis virus (mainly hepatitis virus B and C), development of chronic hepatitis, and liver cancer. The prevention of chronic inflammation is a factor that can prevent cancer, so it effectively inhibits or blocks the occurrence, development, and progression of the chronic inflammation process playing important roles in the prevention of cancer. Monitoring of the causes and inflammatory factors in chronic inflammation processes is a useful way to predict cancer and assess the efficiency of cancer prevention. Chronic inflammation-based biomarkers are useful tools to predict and prevent cancer.
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Affiliation(s)
- Shehua Qian
- 1Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 2Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 3State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
| | - Olga Golubnitschaja
- 4Radiological Clinic, UKB, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Sigmund-Freud-Str 25, 53105 Bonn, Germany
- 5Breast Cancer Research Centre, UKB, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
- 6Centre for Integrated Oncology, Cologne-Bonn, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
| | - Xianquan Zhan
- 1Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 2Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 3State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 7Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan People's Republic of China
- 8National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan People's Republic of China
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13
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Rossi T, Tedaldi G, Petracci E, Abou Khouzam R, Ranzani GN, Morgagni P, Saragoni L, Monti M, Calistri D, Ulivi P, Molinari C. E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer. Int J Mol Sci 2019; 20:ijms20184452. [PMID: 31509966 PMCID: PMC6769612 DOI: 10.3390/ijms20184452] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 09/03/2019] [Accepted: 09/05/2019] [Indexed: 12/24/2022] Open
Abstract
CDH1 gene, encoding E-cadherin, is a tumor suppressor gene frequently altered in gastric cancers (GCs) of both diffuse (DGC) and intestinal (IGC) histotypes, albeit through different mechanisms. The study aimed to characterize CDH1 expression in sporadic IGC and to investigate whether microRNAs (miRs) are involved in its transcriptional control. We evaluated CDH1 expression by quantitative real-time PCR (RT-qPCR) in 33 IGC patients and found a significant downregulation in tumor tissues compared to normal counterparts (p-value = 0.025). Moreover, 14 miRs, predicted to be involved in CDH1 regulation in both a direct and indirect manner, were selected and analyzed by RT-qPCR in an independent case series of 17 IGCs and matched normal tissues. miR-101, miR-26b, and miR-200c emerged as significantly downregulated and were confirmed in the case series of 33 patients (p-value < 0.001). Finally, we evaluated EZH2 expression, a target of both miR-101 and miR-26b, which showed significant upregulation in IGCs (p-value = 0.005). A significant inverse correlation was observed between EZH2 overexpression and CDH1, miR-101, and miR-26b levels (p-value < 0.001). Our results reinforce the link between CDH1 and IGC, highlighting the role of miRs in its transcriptional control and improving our understanding of GC subtypes and biomarkers.
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Affiliation(s)
- Tania Rossi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Gianluca Tedaldi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Elisabetta Petracci
- Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Raefa Abou Khouzam
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
| | | | - Paolo Morgagni
- General and Oncologic Surgery, Department of Surgery, G.B. Morgagni L.Pierantoni General Hospital, AUSL Romagna, 47121 Forlì, Italy.
| | - Luca Saragoni
- Department of Pathology, AUSL Romagna, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy.
| | - Manlio Monti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Daniele Calistri
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Paola Ulivi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
| | - Chiara Molinari
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy.
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14
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Alarcón-Millán J, Martínez-Carrillo DN, Peralta-Zaragoza O, Fernández-Tilapa G. Regulation of GKN1 expression in gastric carcinogenesis: A problem to resolve (Review). Int J Oncol 2019; 55:555-569. [PMID: 31322194 DOI: 10.3892/ijo.2019.4843] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 07/04/2019] [Indexed: 11/05/2022] Open
Abstract
Gastrokine 1 (GKN1) is a protein expressed on the surface mucosa cells of the gastric antrum and fundus, which contributes to maintaining gastric homeostasis, inhibits inflammation and is a tumor suppressor. The expression of GKN1 decreases in mucosa that are either inflamed or infected by Helicobacter pylori, and is absent in gastric cancer. The measurement of circulating GKN1 concentration, the protein itself, or the mRNA in gastric tissue may be of use for the early diagnosis of cancer. The mechanisms that modulate the deregulation or silencing of GKN1 expression have not been completely described. The modification of histones, methylation of the GKN1 promoter, or proteasomal degradation of the protein have been detected in some patients; however, these mechanisms do not completely explain the absence of GKN1 or the reduction in GKN1 levels. Only NKX6.3 transcription factor has been shown to be a positive modulator of GKN1 transcription, although others also have an affinity with sequences in the promoter of this gene. While microRNAs (miRNAs) are able to directly or indirectly regulate the expression of genes at the post‑transcriptional level, the involvement of miRNAs in the regulation of GKN1 has not been reported. The present review analyzes the information reported on the determination of GKN1 expression and the regulation of its expression at the transcriptional, post‑transcriptional and post‑translational levels; it proposes an integrated model that incorporates the regulation of GKN1 expression via transcription factors and miRNAs in H. pylori infection.
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Affiliation(s)
- Judit Alarcón-Millán
- Clinical Research Laboratory, Faculty of Biological Chemical Sciences, Guerrero Autonomous University, Chilpancingo, Guerrero 39070, México
| | - Dinorah Nashely Martínez-Carrillo
- Clinical Research Laboratory, Faculty of Biological Chemical Sciences, Guerrero Autonomous University, Chilpancingo, Guerrero 39070, México
| | - Oscar Peralta-Zaragoza
- Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Cuernavaca, Morelos 62100, México
| | - Gloria Fernández-Tilapa
- Clinical Research Laboratory, Faculty of Biological Chemical Sciences, Guerrero Autonomous University, Chilpancingo, Guerrero 39070, México
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15
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Pereira AL, Magalhães L, Moreira FC, Reis-das-Mercês L, Vidal AF, Ribeiro-Dos-Santos AM, Demachki S, Anaissi AKM, Burbano RMR, Albuquerque P, Dos Santos SEB, de Assumpção PP, Ribeiro-Dos-Santos ÂKC. Epigenetic Field Cancerization in Gastric Cancer: microRNAs as Promising Biomarkers. J Cancer 2019; 10:1560-1569. [PMID: 31031866 PMCID: PMC6485221 DOI: 10.7150/jca.27457] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 11/21/2018] [Indexed: 12/17/2022] Open
Abstract
Background: The biological role of microRNAs (miRNAs) in field cancerization is unknown. To investigate the involvement of miRNAs in gastric field cancerization, we evaluated the expression profile of ten miRNAs and their diagnostic value. Methods: We used three groups of FFPE gastric samples: non-cancer (NC), cancer adjacent (ADJ) and gastric cancer (GC). The expression profiles of hsa-miR-10a, -miR-21, -miR-29c, -miR-135b, -miR-148a, -miR-150, -miR-204, -miR-215, -miR-483 and -miR-664a were investigated using qRT-PCR. The results obtained by qRT-PCR were validated in Small RNA-Seq data from the TCGA database. The search for target genes of the studied miRNAs was performed in the miRTarBase public database and miRTargetLink tool, using experimentally validated interactions. In addition, we also performed the functional analysis of these genes using enrichment in KEGG pathways. The potential as biomarker was evaluated using a receiver operating characteristic (ROC) curve and the derived area under the curve (AUC>0.85) analysis. Results: The miRNAs hsa-miR-10a, -miR-21, -miR-135b, hsa-miR-148a, -miR-150, -miR-215, -miR-204, -miR-483 and -miR-664a were up-regulated in ADJ and GC compared to NC (P<0.03); and hsa-miR-21 and -miR-135b were up-regulated in GC compared to ADJ (P<0.01). Hsa-miR-148a, -miR-150, -miR-215, -miR-483 and -miR-664a were not differentially expressed between GC and ADJ, suggesting that both share similar changes (P>0.1). The TS-miR hsa-miR-29c was up-regulated in ADJ compared to NC and GC (P<0.01); we did not observe a significant difference in the expression of this miRNA between NC and GC. This feature may be an antitumor mechanism used by cancer-adjacent tissue because this miRNA regulates the BCL-2, CDC42 and DMNT3A oncogenes. The expression level of hsa-miR-204 was associated with Helicobacter pylori infection status (P<0.05). Functional analysis using the genes regulated by the studied miRNAs showed that they are involved in biological pathways and cellular processes that are critical for the establishment of H. pylori infection and for the onset, development and progression of GC. hsa-miR-10a, -miR-21, -miR-135b, -miR-148a, -miR-150, -miR-215, -miR-483 and -miR-664a were able to discriminate NC from other tissues with great accuracy (AUC>0.85). Conclusion: The studied miRNAs are closely related to field cancerization, regulate genes important for gastric carcinogenesis and can be potentially useful as biomarkers in GC.
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Affiliation(s)
- Adenilson Leão Pereira
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil
| | - Leandro Magalhães
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil
| | - Fabiano Cordeiro Moreira
- Research Center on Oncology, Institute of Health Sciences, Federal University of Pará, Mundurucus Street, 66073-000, Belém, Pará, Brazil
| | - Laís Reis-das-Mercês
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil
| | - Amanda Ferreira Vidal
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil
| | - André Maurício Ribeiro-Dos-Santos
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil
| | - Samia Demachki
- Research Center on Oncology, Institute of Health Sciences, Federal University of Pará, Mundurucus Street, 66073-000, Belém, Pará, Brazil
| | - Ana Karyssa Mendes Anaissi
- Research Center on Oncology, Institute of Health Sciences, Federal University of Pará, Mundurucus Street, 66073-000, Belém, Pará, Brazil
| | - Rommel Mario Rodríguez Burbano
- Research Center on Oncology, Institute of Health Sciences, Federal University of Pará, Mundurucus Street, 66073-000, Belém, Pará, Brazil
| | - Paulo Albuquerque
- São Camilo and São Luís Hospital, Dr. Marcello Cândia Street, 68901-901, Macapá, Amapá, Brazil
| | - Sidney Emanuel Batista Dos Santos
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil.,Research Center on Oncology, Institute of Health Sciences, Federal University of Pará, Mundurucus Street, 66073-000, Belém, Pará, Brazil
| | - Paulo Pimentel de Assumpção
- Research Center on Oncology, Institute of Health Sciences, Federal University of Pará, Mundurucus Street, 66073-000, Belém, Pará, Brazil
| | - Ândrea Kely Campos Ribeiro-Dos-Santos
- Laboratory of Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Augusto Corrêa Avenue, 66075-110, Belém, Pará, Brazil.,Research Center on Oncology, Institute of Health Sciences, Federal University of Pará, Mundurucus Street, 66073-000, Belém, Pará, Brazil
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16
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Shao L, Chen Z, Soutto M, Zhu S, Lu H, Romero-Gallo J, Peek R, Zhang S, El-Rifai W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer. FASEB J 2018; 33:264-274. [PMID: 29985646 DOI: 10.1096/fj.201701456rr] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression of miR-135b-5p and its role in gastric cancer. We describe the overexpression of miR-135b-5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR-135b-5p is also up-regulated in gastric tumors from the trefoil factor 1-knockout mouse model. Infection with H. pylori induced the expression of miR-135b-5p in the in vitro and in vivo models. miR-135b-5p induction was mediated by NF-κB. Treatment of gastric cancer cells with TNF-α induced miR-135b-5p in a NF-κB-dependent manner. Mechanistically, we found that miR-135b-5p targets Krüppel-like factor 4 (KLF4) and binds to its 3' UTR, leading to reduced KLF4 expression. Functionally, high levels of miR-135b-5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection and miR-135b-5p-KLF4, suggesting that targeting miR-135b-5p could be a potential therapeutic approach to circumvent resistance to cisplatin.-Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero-Gallo, J., Peek, R., Zhang, S., El-Rifai, W. Helicobacter pylori-induced miR-135b-5p promotes cisplatin resistance in gastric cancer.
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Affiliation(s)
- Linlin Shao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Department of Veterans Affairs, Miami Healthcare System, Miami, Florida, USA
| | - Zheng Chen
- Department of Veterans Affairs, Miami Healthcare System, Miami, Florida, USA.,Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA; and
| | - Mohammed Soutto
- Department of Veterans Affairs, Miami Healthcare System, Miami, Florida, USA
| | - Shoumin Zhu
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA; and
| | - Heng Lu
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA; and
| | - Judith Romero-Gallo
- Division of Gastroenterology, Hematology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Richard Peek
- Division of Gastroenterology, Hematology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wael El-Rifai
- Department of Veterans Affairs, Miami Healthcare System, Miami, Florida, USA.,Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA; and
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17
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Zhang J, Ren J, Hao S, Ma F, Xin Y, Jia W, Sun Y, Liu Z, Yu H, Jia J, Li W. MiRNA-491-5p inhibits cell proliferation, invasion and migration via targeting JMJD2B and serves as a potential biomarker in gastric cancer. Am J Transl Res 2018; 10:525-534. [PMID: 29511447 PMCID: PMC5835818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 01/17/2018] [Indexed: 06/08/2023]
Abstract
Our previous work discovered that the histone demethylase JMJD2B (KDM4B) plays oncogenic roles in gastric carcinogenesis, but the regulatory mechanism of JMJD2B in gastric cancer has not been well defined. It has been revealed that microRNAs function as gene regulators by binding to the 3'UTR of mRNAs to inhibit gene expression. In this study, we found that miR-491-5p suppressed cell proliferation, invasion and migration by directly targeting the JMJD2B 3'UTR in gastric cancer. Moreover, miR-491-5p was decreased in GC tissues compared with adjacent normal tissues, and JMJD2B had the inverse expression pattern. In contrast to healthy individuals, GC patients had lower miR-491-5p expression in serum (P<0.0001). Our data indicate that miR-491-5p serves as a tumor suppressor in GC and might be a novel potential biomarker for the detection of gastric cancer.
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Affiliation(s)
- Jinjin Zhang
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Juchao Ren
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
- Department of Urology, Qilu Hospital, Shandong UniversityJinan, PR China
| | - Shengjie Hao
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Fang Ma
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Yan Xin
- Department of Clinical Laboratory, Feicheng Hospital of Traditional Chinese MedicineFeicheng, PR China
| | - Wenxiao Jia
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Yundong Sun
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Zhifang Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Han Yu
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Jihui Jia
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
| | - Wenjuan Li
- Key Laboratory for Experimental Teratology of Chinese Ministry of Education, The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Microbiology, School of Basic Medical Sciences, Shandong UniversityJinan, PR China
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18
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Pagliari M, Munari F, Toffoletto M, Lonardi S, Chemello F, Codolo G, Millino C, Della Bella C, Pacchioni B, Vermi W, Fassan M, de Bernard M, Cagnin S. Helicobacter pylori Affects the Antigen Presentation Activity of Macrophages Modulating the Expression of the Immune Receptor CD300E through miR-4270. Front Immunol 2017; 8:1288. [PMID: 29085364 PMCID: PMC5649134 DOI: 10.3389/fimmu.2017.01288] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 09/25/2017] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori (Hp) is a Gram-negative bacterium that infects the human gastric mucosa, leading to chronic inflammation. If not eradicated with antibiotic treatment, the bacterium persists in the human stomach for decades increasing the risk to develop chronic gastritis, gastroduodenal ulcer, and gastric adenocarcinoma. The lifelong persistence of Hp in the human stomach suggests that the host response fails to clear the infection. It has been recently shown that during Hp infection phagocytic cells promote high Hp loads rather than contributing to bacterial clearance. Within these cells Hp survives in "megasomes," large structures arising from homotypic fusion of phagosomes, but the mechanism that Hp employs to avoid phagocytic killing is not completely understood. Here, we show that Hp infection induces the downregulation of specific microRNAs involved in the regulation of transcripts codifying for inflammatory proteins. miR-4270 targets the most upregulated gene: the immune receptor CD300E, whose expression is strictly dependent on Hp infection. CD300E engagement enhances the pro-inflammatory potential of macrophages, but in parallel it affects their ability to express and expose MHC class II molecules on the plasma membrane, without altering phagocytosis. This effect compromises the possibility for effector T cells to recognize and activate the killing potential of macrophages, which, in turn would become a survival niche for the bacterium. Taken together, our data add another piece to the complicate puzzle represented by the long-life coexistence between Hp and the human host and contribute with new insights toward understanding the regulation and function of the immune receptor CD300E.
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Affiliation(s)
| | - Fabio Munari
- Department of Biomedical Sciences, University of Padua, Venetian Institute of Molecular Medicine (VIMM), Padua, Italy
| | | | - Silvia Lonardi
- Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy
| | - Francesco Chemello
- Department of Biology, University of Padua, Padua, Italy.,CRIBI Biotechnology Center, University of Padua, Padua, Italy
| | - Gaia Codolo
- Department of Biology, University of Padua, Padua, Italy
| | - Caterina Millino
- Department of Biology, University of Padua, Padua, Italy.,CRIBI Biotechnology Center, University of Padua, Padua, Italy
| | | | - Beniamina Pacchioni
- Department of Biology, University of Padua, Padua, Italy.,CRIBI Biotechnology Center, University of Padua, Padua, Italy
| | - William Vermi
- Department of Molecular and Translational Medicine, Section of Pathology, University of Brescia, Brescia, Italy
| | - Matteo Fassan
- Department of Medicine, University of Padua, Padua, Italy
| | | | - Stefano Cagnin
- Department of Biology, University of Padua, Padua, Italy.,CRIBI Biotechnology Center, University of Padua, Padua, Italy
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19
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Lee JW, Kim N, Park JH, Kim HJ, Chang H, Kim JM, Kim JW, Lee DH. Differential MicroRNA Expression Between Gastric Cancer Tissue and Non-cancerous Gastric Mucosa According to Helicobacter pylori Status. J Cancer Prev 2017; 22:33-39. [PMID: 28382284 PMCID: PMC5380187 DOI: 10.15430/jcp.2017.22.1.33] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 03/15/2017] [Accepted: 03/15/2017] [Indexed: 12/28/2022] Open
Abstract
Background MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to Helicobacter pylori status. Methods Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n = 8) or H. pylori-negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without H. pylori. And then, expression levels of miRNAs were compared according to subgroups. Results A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, P < 0.05) in cancer tissue, compared to noncancerous mucosa in both of H. pylori-negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at H. pylori-negative group. For H. pylori-positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of H. pylori-negative and -positive. Conclusions miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to H. pylori status.
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Affiliation(s)
- Jung Won Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine, Samsung Changwon Hospital, Changwon, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Jin Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine, Myongji Hospital, Goyang, Korea
| | - Hyun Chang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jung Min Kim
- NAR Center, Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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20
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Singh S, Jha HC. Status of Epstein-Barr Virus Coinfection with Helicobacter pylori in Gastric Cancer. JOURNAL OF ONCOLOGY 2017; 2017:3456264. [PMID: 28421114 PMCID: PMC5379099 DOI: 10.1155/2017/3456264] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 02/14/2017] [Indexed: 12/14/2022]
Abstract
Epstein-Barr virus is a ubiquitous human herpesvirus whose primary infection causes mononucleosis, Burkett's lymphoma, nasopharyngeal carcinoma, autoimmune diseases, and gastric cancer (GC). The persistent infection causes malignancies in lymph and epithelial cells. Helicobacter pylori causes gastritis in human with chronic inflammation. This chronic inflammation is thought to be the cause of genomic instability. About 45%-word population have a probability of having both pathogens, namely, H. pylori and EBV. Approximately 180 per hundred thousand population is developing GC along with many gastric abnormalities. This makes GC the third leading cause of cancer-related death worldwide. Although lots of research are carried out individually for EBV and H. pylori, still there are very few reports available on coinfection of both pathogens. Recent studies suggested that EBV and H. pylori coinfection increases the occurrence of GC as well as the early age of GC detection comparing to individual infection. The aim of this review is to present status on coinfection of both pathogens and their association with GC.
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Affiliation(s)
- Shyam Singh
- Centre for Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, India
| | - Hem Chandra Jha
- Centre for Biosciences and Biomedical Engineering, Indian Institute of Technology, Indore, India
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21
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Chen SY, Zhang RG, Duan GC. Pathogenic mechanisms of the oncoprotein CagA in H. pylori-induced gastric cancer (Review). Oncol Rep 2016; 36:3087-3094. [PMID: 27748858 DOI: 10.3892/or.2016.5145] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 09/16/2016] [Indexed: 11/06/2022] Open
Abstract
Infection with Helicobacter pylori is the strongest risk factor for the development of chronic gastritis, gastric ulcer and gastric carcinoma. The majority of the H. pylori-infected population remains asymptomatic, and only 1% of individuals may progress to gastric cancer. The clinical outcomes caused by H. pylori infection are considered to be associated with bacterial virulence, genetic polymorphism of hosts as well as environmental factors. Most H. pylori strains possess a cytotoxin-associated gene (cag) pathogenicity island (cagPAI), encoding a 120-140 kDa CagA protein, which is the most important bacterial oncoprotein. CagA is translocated into host cells via T4SS system and affects the expression of signaling proteins in a phosphorylation-dependent and independent manner. Thus, this review summarizes the results of relevant studies, discusses the pathogenesis of CagA-mediated gastric cancer.
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Affiliation(s)
- Shuai-Yin Chen
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Rong-Guang Zhang
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Guang-Cai Duan
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
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22
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Rossi AFT, Cadamuro ACT, Biselli-Périco JM, Leite KRM, Severino FE, Reis PP, Cordeiro JA, Silva AE. Interaction between inflammatory mediators and miRNAs in Helicobacter pylori infection. Cell Microbiol 2016; 18:1444-58. [PMID: 26945693 PMCID: PMC5074252 DOI: 10.1111/cmi.12587] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Revised: 02/12/2016] [Accepted: 02/29/2016] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori cause chronic inflammation favouring gastric carcinogenesis, and its eradication may prevent malignant transformation. We evaluated whether H. pylori infection and its eradication modify the expression of inflammatory mediators in patients with chronic gastritis. Furthermore, we assessed whether microRNAs modulate inflammatory pathways induced by H. pylori and identified miRNA–gene interaction networks. mRNA and protein expression of TNFA, IL6, IL1B, IL12A, IL2 and TGFBRII and miRNAs miR‐103a‐3p, miR‐181c‐5p, miR‐370‐3p, miR‐375 and miR‐223‐3p were evaluated in tissue samples from 20 patients with chronic gastritis H. pylori negative (Hp−) and 31 H. pylori positive (Hp+), before and three months after bacterium eradication therapy, in comparison with a pool of Hp− normal gastric mucosa. Our results showed that H. pylori infection leads to up‐regulation of TNFA, IL6, IL12A and IL2 and down‐regulation of miRNAs. Bacterium eradication reduces the expression of TNFA and IL6 and up‐regulates TGFBRII and all investigated miRNAs, except miR‐223‐3p. Moreover, transcriptional profiles of inflammatory mediators and miRNAs after eradication are different from the non‐infected group. Deregulated miRNA–mRNA interaction networks were observed in the Hp+ group before and after eradication. Therefore, miRNAs modulated cytokine expression in the presence of H. pylori and after its eradication, suggesting that miRNAs participate in the pathological process triggered by H. pylori in the gastric mucosa.
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Affiliation(s)
- Ana Flávia Teixeira Rossi
- UNESP, São Paulo State University, Department of Biology, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, Brazil
| | - Aline Cristina Targa Cadamuro
- UNESP, São Paulo State University, Department of Biology, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, Brazil
| | - Joice Matos Biselli-Périco
- UNESP, São Paulo State University, Department of Biology, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, Brazil
| | - Kátia Ramos Moreira Leite
- USP, São Paulo University, Faculty of Medicine, Department of Surgery, Avenida Dr. Arnaldo, 455, São Paulo, SP, Brazil
| | - Fábio Eduardo Severino
- UNESP, São Paulo State University, Faculty of Medicine, Department of Surgery and Orthopedics, Avenida Prof. Montenegro, Botucatu, SP, Brazil
| | - Patricia P Reis
- UNESP, São Paulo State University, Faculty of Medicine, Department of Surgery and Orthopedics, Avenida Prof. Montenegro, Botucatu, SP, Brazil
| | - José Antonio Cordeiro
- UNESP, São Paulo State University, Department of Biology, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, Brazil
| | - Ana Elizabete Silva
- UNESP, São Paulo State University, Department of Biology, Rua Cristóvão Colombo, 2265, São José do Rio Preto, SP, Brazil.
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23
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Tulay P, Sengupta SB. MicroRNA expression and its association with DNA repair in preimplantation embryos. J Reprod Dev 2016; 62:225-34. [PMID: 26853522 PMCID: PMC4919285 DOI: 10.1262/jrd.2015-167] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Active DNA repair pathways are crucial for preserving genomic integrity and are likely among the complex
mechanisms involved in the normal development of preimplantation embryos. MicroRNAs (miRNA), short non-coding
RNAs, are key regulators of gene expression through the post-transcriptional and post-translational
modification of mRNA. The association of miRNA expression with infertility or polycystic ovarian syndrome has
been widely investigated; however, there are limited data regarding the importance of miRNA regulation in DNA
repair during preimplantation embryo development. In this article, we review normal miRNA biogenesis and
consequences of aberrant miRNA expression in the regulation of DNA repair in gametes and preimplantation
embryos.
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Affiliation(s)
- Pinar Tulay
- Near East University, Faculty of Medicine, Department of Medical Genetics, Nicosia, Cyprus
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24
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Valenzuela MA, Canales J, Corvalán AH, Quest AFG. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. World J Gastroenterol 2015; 21:12742-12756. [PMID: 26668499 PMCID: PMC4671030 DOI: 10.3748/wjg.v21.i45.12742] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 08/08/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
The sequence of events associated with the development of gastric cancer has been described as “the gastric precancerous cascade”. This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context.
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25
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Libânio D, Dinis-Ribeiro M, Pimentel-Nunes P. Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions. World J Clin Oncol 2015; 6:111-132. [PMID: 26468448 PMCID: PMC4600186 DOI: 10.5306/wjco.v6.i5.111] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2015] [Revised: 06/22/2015] [Accepted: 08/04/2015] [Indexed: 02/06/2023] Open
Abstract
The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori (H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. MicroRNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify microRNA expression in the gastric mucosa and microRNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. MicroRNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor microRNAs. Furthermore, microRNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, microRNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each microRNA can control the expression of hundreds to thousands of genes, knowledge of microRNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of microRNAs in H. pylori gastric carcinogenesis, identifying the microRNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.
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26
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Tulay P, Naja RP, Cascales-Roman O, Doshi A, Serhal P, SenGupta SB. Investigation of microRNA expression and DNA repair gene transcripts in human oocytes and blastocysts. J Assist Reprod Genet 2015; 32:1757-64. [PMID: 26438643 DOI: 10.1007/s10815-015-0585-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 09/23/2015] [Indexed: 12/13/2022] Open
Abstract
PURPOSE The aim of the study is to investigate the regulation of DNA repair genes by microRNAs (miRNAs). miRNAs are short non-coding RNAs that regulate transcriptional and post-transcriptional gene silencing. Several miRNAs that are expressed during preimplantation embryo development have been shown or are predicted to target genes that regulate cell cycle checkpoints and DNA repair in response to DNA damage. METHODS This study compares the expression level of 20 miRNAs and 9 target transcripts involved in DNA repair. The statistical significance of differential miRNA expression between oocytes and blastocysts was determined by t test analysis using the GraphPad Prism v6 software. The possible regulatory roles of miRNAs on their target messenger RNAs (mRNAs) were analysed using a Pearson correlation test. RESULTS This study shows for the first time that several miRNAs are expressed in human oocytes and blastocysts that target key genes involved in DNA repair and cell cycle checkpoints. Blastocysts exhibited statistically significant lower expression levels for the majority of miRNAs compared to oocytes (p < 0.05). Correlation analyses showed that there was both inverse and direct association between miRNAs and their target mRNAs. CONCLUSIONS miRNAs target many mRNAs including ones involved in DNA repair mechanisms. This study suggests that miRNAs and their target mRNAs involved in DNA repair are expressed in preimplantation embryos. Similar to the miRNAs expressed in adult tissues, these miRNAs seem to have regulatory roles on their target DNA repair mRNAs during preimplantation embryo development.
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Affiliation(s)
- P Tulay
- Faculty of Medicine, Medical Genetics Department, Near East University, Yakin Dogu Bulvari, Nicosia, Cyprus. .,UCL Centre for PGD, Institute for Women's Health, University College London, London, UK.
| | - R P Naja
- UCL Centre for PGD, Institute for Women's Health, University College London, London, UK
| | - O Cascales-Roman
- UCL Centre for PGD, Institute for Women's Health, University College London, London, UK
| | - A Doshi
- The Centre for Reproductive and Genetic Health, University College Hospital, The New Wing Eastman Dental Hospital, London, UK
| | - P Serhal
- The Centre for Reproductive and Genetic Health, University College Hospital, The New Wing Eastman Dental Hospital, London, UK
| | - S B SenGupta
- UCL Centre for PGD, Institute for Women's Health, University College London, London, UK
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27
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Link A, Schirrmeister W, Langner C, Varbanova M, Bornschein J, Wex T, Malfertheiner P. Differential expression of microRNAs in preneoplastic gastric mucosa. Sci Rep 2015; 5:8270. [PMID: 25652892 PMCID: PMC4317705 DOI: 10.1038/srep08270] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 01/14/2015] [Indexed: 12/14/2022] Open
Abstract
Gastric carcinogenesis is a multifactorial H.pylori-triggered dynamic process that goes through a cascade of preneoplastic conditions. The expression of miRNAs in the stomach with regard to preneoplastic precursor conditions and H.pylori infection has not been investigated systematically. In this prospective proof-of-principle study, we evaluated the miRNA expression in gastric antrum and corpus mucosa from patients with chronic non-atrophic gastritis (CNAG), atrophic gastritis (AG), and GC compared to controls. Gastric normal mucosa shows a unique expression pattern for miR-21, miR-155 and miR-223, which is specific for different regions. In correlation with progression of Correa's cascade and H.pylori infection, we observed a gradual increase in miR-155 and miR-223 both in corpus and antrum and miR-21 only in the antrum mucosa. Using miRNA expression we calculated a score that allowed us to discriminate patients with AG from subjects with normal mucosa with high diagnostic accuracy in testing and validation cohorts reproducibly. In summary, the expression pattern of miRNAs in the gastric mucosa is gradually increased with progression of Correa's cascade and H.pylori infection, suggesting miRNAs as potential biomarkers for preneoplastic precursor conditions. However, differences of miRNA expression between the gastric antrum and the corpus need to be considered in future studies.
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Affiliation(s)
- Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Wiebke Schirrmeister
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Cosima Langner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Mariya Varbanova
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Jan Bornschein
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Thomas Wex
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
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28
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Zhai R, Wei Y, Su L, Liu G, Kulke MH, Wain JC, Christiani DC. Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of Helicobacter pylori infection status. Carcinogenesis 2014; 36:87-93. [PMID: 25381453 DOI: 10.1093/carcin/bgu228] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Cell free circulating microRNAs (cfmiRNAs) have been recognized as robust and stable biomarkers of cancers. However, little is known about the prognostic significance of cfmiRNAs in esophageal adenocarcinoma (EA). In this study, we explored whether specific cfmiRNA profiles could predict EA prognosis and whether Helicobacter pylori (HP) infection status could influence the association between cfmiRNAs and EA survival outcome. We profiled 1075 miRNAs in pooled serum samples from 30 EA patients and 30 healthy controls. The most relevant cfmiRNAs were then assessed for their associations with EA survival in an independent cohort of 82 patients, using Log-rank test and multivariate Cox regression models. Quantitative real-time PCR (qRT-PCR) was used for cfmiRNA profiling. HP infection status was determined by immunoblotting assay. We identified a panel of 18 cfmiRNAs that could distinguish EA patients from healthy subjects (P = 3.0E-12). In overall analysis and in HP-positive subtype patients, no cfmiRNA was significantly associated with EA prognosis. In HP-negative patients, however, 15 cfmiRNAs were significantly associated with overall survival (OS) (all P < 0.05). A combined 2-cfmiRNA (low miR-3935 and high miR-4286) risk score was constructed; that showed greater risk for worse OS (HR = 2.22, P = 0.0019) than individual cfmiRNA alone. Patients with high-risk score had >10-fold increased risk of death than patients with low risk score (P = 0.0302; HR = 10.91; P = 0.0094). Our findings suggest that dysregulated cfmiRNAs may contribute to EA survival outcome and HP infection status may modify the association between cfmiRNAs and EA survival.
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Affiliation(s)
- Rihong Zhai
- Shenzhen Key Laboratory of Translational Medicine of Tumor, Shenzhen University School of Medicine, Shenzhen 518060, China, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA, Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital, Toronto, Ontario M5G 2C4, Canada, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA and Department of Surgery and Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Yongyue Wei
- Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
| | - Li Su
- Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
| | - Geoffrey Liu
- Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital, Toronto, Ontario M5G 2C4, Canada
| | - Mathew H Kulke
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA and
| | | | - David C Christiani
- Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital, Toronto, Ontario M5G 2C4, Canada, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
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29
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Ishiguro H, Kimura M, Takeyama H. Role of microRNAs in gastric cancer. World J Gastroenterol 2014; 20:5694-5699. [PMID: 24914330 PMCID: PMC4024779 DOI: 10.3748/wjg.v20.i19.5694] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 12/11/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Although gastric cancer (GC) is one of the leading causes of cancer-related death, major therapeutic advances have not been made, and patients with GC still face poor outcomes. The prognosis of GC also remains poor because the molecular mechanisms of GC progression are incompletely understood. MicroRNAs (miRNAs) are noncoding RNAs that are associated with gastric carcinogenesis. Studies investigating the regulation of gene expression by miRNAs have made considerable progress in recent years, and abnormalities in miRNA expression have been shown to be associated with the occurrence and progression of GC. miRNAs contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors, affecting cell proliferation, apoptosis, motility, and invasion. Moreover, a number of miRNAs have been shown to be associated with tumor type, tumor stage, and patient survival and therefore may be developed as novel diagnostic or prognostic markers. In this review, we discuss the involvement of miRNAs in GC and the mechanisms through which they regulate gene expression and biological functions. Then, we review recent research on the involvement of miRNAs in GC prognosis, their potential use in chemotherapy, and their effects on Helicobacter pylori infections in GC. A greater understanding of the roles of miRNAs in gastric carcinogenesis could provide insights into the mechanisms of tumor development and could help to identify novel therapeutic targets.
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30
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Kuo CH, Weng BC, Wu CC, Yang SF, Wu DC, Wang YC. Apigenin has anti-atrophic gastritis and anti-gastric cancer progression effects in Helicobacter pylori-infected Mongolian gerbils. JOURNAL OF ETHNOPHARMACOLOGY 2014; 151:1031-1039. [PMID: 24374236 DOI: 10.1016/j.jep.2013.11.040] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Revised: 11/19/2013] [Accepted: 11/20/2013] [Indexed: 06/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Apigenin, one of the most common flavonoids, is abundant in celery, parsley, chamomile, passionflower, and other vegetables and fruits. Celery is recognized as a medicinal vegetable in Oriental countries to traditionally treat inflammation, swelling, blood pressure, serum lipid, and toothache. In this study, we investigated apigenin treatment effects on Helicobacter pylori-induced atrophic gastritis and gastric cancer progression in Mongolian gerbils. MATERIALS AND METHODS Five to eight-week-old Mongolian gerbils were inoculated with Helicobacter pylori for four weeks without (atrophic gastritis group) or with N'-methyl-N'-nitro-N-nitroso-guanidine (MNNG) (gastric cancer group) in drinking water, and were then rested for two weeks. During the 7th-32th (atrophic gastritis group) or the 7th-52th (gastric cancer group) weeks, they were given various doses (0-60 mg/kgbw/day) of apigenin. At the end of the 32th (atrophic gastritis group) or the 52th (atrophic gastritis group) week, all Mongolian gerbils were sacrificed using the CO2 asphyxia method. The histological changes of Helicobacter pylori colonization, neutrophil and monocyte infiltrations, and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils were examined using immunohistochemistry stain and Sydney System scoring. RESULTS Apigenin treatments (30-60 mg/kgbw/day) effectively decreased atrophic gastritis (atrophic gastritis group) and dysplasia/gastric cancer (gastric cancer group) rates in Mongolian gerbils. Apigenin treatment (60 mg/kgbw/day) significantly decreased Helicobacter pylori colonization and Helicobacter pylori-induced histological changes of neutrophil and monocyte infiltrations and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils. CONCLUSIONS Apigenin has the remarkable ability to inhibit Helicobacter pylori-induced atrophic gastritis and gastric cancer progression as well as possessing potent anti-gastric cancer activity.
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Affiliation(s)
- Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Bi-Chuang Weng
- Division of Gastroenterology, Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Chun-Chieh Wu
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
| | - Sheau-Fang Yang
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, ROC
| | - Deng-Chang Wu
- Division of Gastroenterology, Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
| | - Yuan-Chuen Wang
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC.
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31
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Shiratsu K, Higuchi K, Nakayama J. Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach. Cancer Sci 2014; 105:126-33. [PMID: 24138592 PMCID: PMC4317868 DOI: 10.1111/cas.12305] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2013] [Revised: 10/08/2013] [Accepted: 10/16/2013] [Indexed: 12/25/2022] Open
Abstract
Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma.
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Affiliation(s)
- Kazuo Shiratsu
- Department of Molecular Pathology, Shinshu University Graduate School of MedicineMatsumoto, Japan
- Department of Gastroenterology, Aizawa HospitalMatsumoto, Japan
| | - Kayoko Higuchi
- Department of Pathology, Aizawa HospitalMatsumoto, Japan
| | - Jun Nakayama
- Department of Molecular Pathology, Shinshu University Graduate School of MedicineMatsumoto, Japan
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Noto JM, Piazuelo MB, Chaturvedi R, Bartel CA, Thatcher EJ, Delgado A, Romero-Gallo J, Wilson KT, Correa P, Patton JG, Peek RM. Strain-specific suppression of microRNA-320 by carcinogenic Helicobacter pylori promotes expression of the antiapoptotic protein Mcl-1. Am J Physiol Gastrointest Liver Physiol 2013; 305:G786-96. [PMID: 24136787 PMCID: PMC3882435 DOI: 10.1152/ajpgi.00279.2013] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Helicobacter pylori is the strongest risk factor for gastric cancer, and strains harboring the cag pathogenicity island, which translocates the oncoprotein CagA into host cells, further augment cancer risk. We previously reported that in vivo adaptation of a noncarcinogenic H. pylori strain (B128) generated a derivative strain (7.13) with the ability to induce adenocarcinoma, providing a unique opportunity to define mechanisms that mediate gastric carcinogenesis. MicroRNAs (miRNAs) are small noncoding RNAs that regulate expression of oncogenes or tumor suppressors and are frequently dysregulated in carcinogenesis. To identify miRNAs and their targets involved in H. pylori-mediated carcinogenesis, miRNA microarrays were performed on RNA isolated from gastric epithelial cells cocultured with H. pylori strains B128, 7.13, or a 7.13 cagA(-) isogenic mutant. Among 61 miRNAs differentially expressed in a cagA-dependent manner, the tumor suppressor miR-320 was significantly downregulated by strain 7.13. Since miR-320 negatively regulates the antiapoptotic protein Mcl-1, we demonstrated that H. pylori significantly induced Mcl-1 expression in a cagA-dependent manner and that suppression of Mcl-1 results in increased apoptosis. To extend these results, mice were challenged with H. pylori strain 7.13 or its cagA(-) mutant; consistent with cell culture data, H. pylori induced Mcl-1 expression in a cagA-dependent manner. In human subjects, cag(+) strains induced significantly higher levels of Mcl-1 than cag(-) strains, and Mcl-1 expression levels paralleled the severity of neoplastic lesions. Collectively, these results indicate that H. pylori suppresses miR-320, upregulates Mcl-1, and decreases apoptosis in a cagA-dependent manner, which likely confers an increased risk for gastric carcinogenesis.
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Affiliation(s)
- Jennifer M. Noto
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee;
| | - M. Blanca Piazuelo
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee;
| | - Rupesh Chaturvedi
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee;
| | - Courtney A. Bartel
- 2Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee;
| | | | - Alberto Delgado
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee;
| | - Judith Romero-Gallo
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee;
| | - Keith T. Wilson
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee; ,3Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee; ,4Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee; and ,5Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee
| | - Pelayo Correa
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee;
| | - James G. Patton
- 2Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee;
| | - Richard M. Peek
- 1Department of Medicine, Division of Gastroenterology, Vanderbilt University, Nashville, Tennessee; ,3Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee;
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33
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Stein M, Ruggiero P, Rappuoli R, Bagnoli F. Helicobacter pylori CagA: From Pathogenic Mechanisms to Its Use as an Anti-Cancer Vaccine. Front Immunol 2013; 4:328. [PMID: 24133496 PMCID: PMC3796731 DOI: 10.3389/fimmu.2013.00328] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Accepted: 09/25/2013] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human population, causing chronic inflammation, which however is largely asymptomatic. Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Chronic exposure to the pathogen and its ability to induce epithelial to mesenchymal transition (EMT) through the injection of cytotoxin-associated gene A into gastric epithelial cells may be key triggers of carcinogenesis. By deregulating cell-cell and cell-matrix interactions as well as DNA methylation, histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT can actively contribute to early stages of the cancer formation. Host response to the infection significantly contributes to disease development and the concomitance of particular genotypes of both pathogen and host may turn into the most severe outcomes. T regulatory cells (Treg) have been recently demonstrated to play an important role in H. pylori-related disease development and at the same time the Treg-induced tolerance has been proposed as a possible mechanism that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori infection has significantly dropped. Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood. In spite of promising results obtained in animal models of infection with a number of vaccine candidates, few clinical trials have been conducted so far and with no satisfactory outcomes. However, prophylactic vaccination may be the only means to efficiently prevent H. pylori-associated cancers.
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Affiliation(s)
- Markus Stein
- Albany College of Pharmacy and Health Sciences, Albany, NY, USA
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34
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Nishizawa T, Suzuki H. The role of microRNA in gastric malignancy. Int J Mol Sci 2013; 14:9487-96. [PMID: 23629677 PMCID: PMC3676795 DOI: 10.3390/ijms14059487] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Revised: 04/19/2013] [Accepted: 04/25/2013] [Indexed: 12/30/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is the main cause of gastritis, gastro-duodenal ulcer, and gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous silencers of numerous target genes. Many miRNA genes are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Recent discoveries have shed new light on the involvement of miRNAs in gastric malignancy. However, at the same time, several miRNAs have been associated with opposing events, leading to reduced inflammation, inhibition of malignancy, and increased apoptosis of transformed cells. The regulation of miRNA expression could be a novel strategy in the chemoprevention of human gastric malignancy. In this article, the biological importance of miRNAs in gastric malignancy is summarized.
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Affiliation(s)
- Toshihiro Nishizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; E-Mail:
- Division of Gastroenterology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; E-Mail:
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35
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Merrell DS, Stintzi A. Research advances in the study of Campylobacter, Helicobacter, and related organisms. Front Cell Infect Microbiol 2012; 2:159. [PMID: 23267439 PMCID: PMC3525878 DOI: 10.3389/fcimb.2012.00159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 11/28/2012] [Indexed: 01/22/2023] Open
Affiliation(s)
- D. Scott Merrell
- Department of Microbiology and Immunology, Uniformed Services UniversityBethesda, MD, USA
- *Correspondence: ;
| | - Alain Stintzi
- Department of Biochemistry, Microbiology and Immunology, University of OttawaOttawa, ON, Canada
- *Correspondence: ;
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