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1
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Chen S, Lei Z, Sun T. The critical role of miRNA in bacterial zoonosis. Int Immunopharmacol 2024; 143:113267. [PMID: 39374566 DOI: 10.1016/j.intimp.2024.113267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 08/21/2024] [Accepted: 09/24/2024] [Indexed: 10/09/2024]
Abstract
The public's health and the financial sustainability of international societies remain threatened by bacterial zoonoses, with limited reliable diagnostic and therapeutic options available for bacterial diseases. Bacterial infections influence mammalian miRNA expression in host-pathogen interactions. In order to counteract bacterial infections, miRNAs participate in gene-specific expression and play important regulatory roles that rely on translational inhibition and target gene degradation by binding to the 3' non-coding region of target genes. Intriguingly, according to current studies, that exogenous miRNAs derived from plants could potentially serve as effective medicinal components sourced from traditional Chinese medicine plants. These exogenous miRNAs exhibit stable functionality in mammals and mimic the regulatory roles of endogenous miRNAs, illuminating the molecular processes behind the therapeutic effects of plants. This review details the immune defense mechanisms of inflammation, apoptosis, autophagy and cell cycle disturbance caused by some typical bacterial infections, summarizes the role of some mammalian miRNAs in regulating these mechanisms, and introduces the cGAS-STING signaling pathway in detail. Evidence suggests that this newly discovered immune defense mechanism in mammalian cells can also be affected by miRNAs. Meanwhile, some examples of transboundary regulation of mammalian mRNA and even bacterial diseases by exogenous miRNAs from plants are also summarized. This viewpoint provides fresh understanding of microbial tactics and host mechanisms in the management of bacterial illnesses.
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Affiliation(s)
- Si Chen
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China
| | - Zhixin Lei
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
| | - Taolei Sun
- School of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of Nanomedicine for Neurodegenerative Disease, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
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2
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Zou J, Xu B, Luo P, Chen T, Duan H. Non-coding RNAs in bladder cancer, a bridge between gut microbiota and host? Front Immunol 2024; 15:1482765. [PMID: 39628486 PMCID: PMC11611751 DOI: 10.3389/fimmu.2024.1482765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Accepted: 10/30/2024] [Indexed: 12/06/2024] Open
Abstract
In recent years, the role of gut microbiota (GM) in bladder cancer has attracted significant attention. Research indicates that GM not only contributes to bladder carcinogenesis but also influences the efficacy of adjuvant therapies for bladder cancer. Despite this, interventions targeting GM have not been widely employed in the prevention and treatment of bladder cancer, mainly due to the incomplete understanding of the complex interactions between the host and gut flora. Simultaneously, aberrantly expressed non-coding RNAs (ncRNAs) have been frequently associated with bladder cancer, playing crucial roles in processes such as cell proliferation, invasion, and drug resistance. It is widely known that the regulation of GM-mediated host pathophysiological processes is partly regulated through epigenetic pathways. At the same time, ncRNAs are increasingly regarded as GM signaling molecules involved in GM-mediated epigenetic regulation. Accordingly, this review analyzes the ncRNAs that are closely related to the GM in the context of bladder cancer occurrence and treatment, and summarizes the role of their interaction with the GM in bladder cancer-related phenotypes. The aim is to delineate a regulatory network between GM and ncRNAs and provide a new perspective for the study and prevention of bladder cancer.
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Affiliation(s)
- Jun Zou
- Department of Otorhinolaryngology, The Affiliated Fengcheng Hospital of Yichun University, Fengcheng, Jiangxi, China
| | - Baisheng Xu
- Department of Urology, The First People's Hospital of Xiushui, Jiujiang, Jiangxi, China
| | - Peiyue Luo
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Tao Chen
- The First Clinical College, Gannan Medical University, Ganzhou, Jiangxi, China
| | - Huanglin Duan
- Department of Urology, The First People's Hospital of Xiushui, Jiujiang, Jiangxi, China
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3
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Xu H, Huang K, Shi M, Gong H, Han M, Tian W, Wang X, Zhang D. MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application. Pharmacol Res 2024; 205:107216. [PMID: 38761883 DOI: 10.1016/j.phrs.2024.107216] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 05/10/2024] [Accepted: 05/11/2024] [Indexed: 05/20/2024]
Abstract
Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.
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Affiliation(s)
- Huimei Xu
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Ke Huang
- Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Mingxuan Shi
- Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, School of Stomatology, Lanzhou University, Lanzhou 730030, China
| | - Hang Gong
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Mengyu Han
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Wenji Tian
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China
| | - Xiaoying Wang
- Department of Emergency, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
| | - Dekui Zhang
- Department of Gastroenterology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China; Key Laboratory of Digestive Diseases, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
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Liu Z, Li H, Huang X, Liu Q. Animal Models of Helicobacter pylori Infection and Vaccines: Current Status and Future Prospects. Helicobacter 2024; 29:e13119. [PMID: 39108210 DOI: 10.1111/hel.13119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 07/10/2024] [Accepted: 07/23/2024] [Indexed: 01/02/2025]
Abstract
Helicobacter pylori infection causes chronic gastritis, ulcers, and gastric cancer, making it a threat to human health. Despite the use of antibiotic therapy, the global prevalence of H. pylori infection remains high, necessitating early eradication measures. Immunotherapy, especially vaccine development, is a promising solution in this direction, albeit the selection of an appropriate animal model is critical in efficient vaccine production. Accordingly, we conducted a literature, search and summarized the commonly used H. pylori strains, H. pylori infection-related animal models, and models for evaluating H. pylori vaccines. Based on factors such as the ability to replicate human diseases, strain compatibility, vaccine types, and eliciting of immune responses, we systematically compared the advantages and disadvantages of different animal models, to obtain the informed recommendations. In addition, we have proposed novel perspectives on H. pylori-related animal models to advance research and vaccine evaluation for the prevention and treatment of diseases such as gastric cancer.
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Affiliation(s)
- Zhili Liu
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
- HuanKui Academy, Nanchang University, Nanchang, China
| | - He Li
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xiaotian Huang
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Qiong Liu
- Department of Medical Microbiology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
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Huang BS, Chen CT, Yeh CC, Fan TY, Chen FY, Liou JM, Shun CT, Wu MS, Chow LP. miR-21 Targets ASPP2 to Inhibit Apoptosis via CHOP-Mediated Signaling in Helicobacter pylori-Infected Gastric Cancer Cells. JOURNAL OF ONCOLOGY 2023; 2023:6675265. [PMID: 37547633 PMCID: PMC10403333 DOI: 10.1155/2023/6675265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 06/05/2023] [Accepted: 06/21/2023] [Indexed: 08/08/2023]
Abstract
Helicobacter pylori (H. pylori) infection affects cell survival pathways, including apoptosis and proliferation in host cells, and disruption of this balance is the key event in the development of H. pylori-induced gastric cancer (HPGC). H. pylori infection induces alterations in microRNAs expression that may be involved in GC development. Bioinformatic analysis showed that microRNA-21 (miR-21) is significantly upregulated in HPGC. Furthermore, quantitative proteomics and in silico prediction were employed to identify potential targets of miR-21. Following functional enrichment and clustered interaction network analyses, five candidates of miR-21 targets, PDCD4, ASPP2, DAXX, PIK3R1, and MAP3K1, were found across three functional clusters in association with cell death and survival, cellular movement, and cellular growth and proliferation. ASPP2 is inhibited by H. pylori-induced miR-21 overexpression. Moreover, ASPP2 levels are inversely correlated with miR-21 levels in HPGC tumor tissues. Thus, ASPP2 was identified as a miR-21 target in HPGC. Here, we observed that H. pylori-induced ASPP2 suppression enhances resistance to apoptosis in GC cells using apoptosis assays. Using protein interaction network and coimmunoprecipitation assay, we identified CHOP as a direct mediator of the ASPP2 proapoptotic activity in H. pylori-infected GC cells. Mechanistically, ASPP2 suppression promotes p300-mediated CHOP degradation, in turn inhibiting CHOP-mediated transcription of Noxa, Bak, and suppression of Bcl-2 to enact antiapoptosis in the GC cells after H. pylori infection. Clinicopathological analysis revealed correlations between decreased ASPP2 expression and higher HPGC risk and poor prognosis. In summary, the discovery of H. pylori-induced antiapoptosis via miR-21-mediated suppression of ASPP2/CHOP-mediated signaling provides a novel perspective for developing HPGC management and treatment.
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Affiliation(s)
- Bo-Shih Huang
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chih-Ta Chen
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chao-Chi Yeh
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ting-Yu Fan
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Fang-Yun Chen
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Lu-Ping Chow
- Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
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Kashyap D, Rele S, Bagde PH, Saini V, Chatterjee D, Jain AK, Pandey RK, Jha HC. Comprehensive insight into altered host cell-signaling cascades upon Helicobacter pylori and Epstein-Barr virus infections in cancer. Arch Microbiol 2023; 205:262. [PMID: 37310490 DOI: 10.1007/s00203-023-03598-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/14/2023]
Abstract
Cancer is characterized by mutagenic events that lead to disrupted cell signaling and cellular functions. It is one of the leading causes of death worldwide. Literature suggests that pathogens, mainly Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with the etiology of human cancer. Notably, their co-infection may lead to gastric cancer. Pathogen-mediated DNA damage could be the first and crucial step in the carcinogenesis process that modulates numerous cellular signaling pathways. Altogether, it dysregulates the metabolic pathways linked with cell growth, apoptosis, and DNA repair. Modulation in these pathways leads to abnormal growth and proliferation. Several signaling pathways such RTK, RAS/MAPK, PI3K/Akt, NFκB, JAK/STAT, HIF1α, and Wnt/β-catenin are known to be altered in cancer. Therefore, this review focuses on the oncogenic roles of H. pylori, EBV, and its associated signaling cascades in various cancers. Scrutinizing these signaling pathways is crucial and may provide new insights and targets for preventing and treating H. pylori and EBV-associated cancers.
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Affiliation(s)
- Dharmendra Kashyap
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | - Samiksha Rele
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | - Pranit Hemant Bagde
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | - Vaishali Saini
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India
| | | | | | - Rajan Kumar Pandey
- Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177, Solna, Sweden
| | - Hem Chandra Jha
- Lab No. POD 1B 602, Infection Bio-Engineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, 453552, India.
- Centre for Rural Development and Technology, Indian Institute of Technology Indore, Madhya Pradesh, 453552, Indore, India.
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7
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Tong T, Zhou Y, Huang Q, Xiao C, Bai Q, Deng B, Chen L. The regulation roles of miRNAs in Helicobacter pylori infection. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2023:10.1007/s12094-023-03094-9. [PMID: 36781601 DOI: 10.1007/s12094-023-03094-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 01/17/2023] [Indexed: 02/15/2023]
Abstract
Helicobacter pylori is a kind of Gram-negative bacteria that parasitizes on human gastric mucosa. Helicobacter pylori infection is very common in human beings, which often causes gastrointestinal diseases, including chronic gastritis, duodenal ulcer and gastric cancer. MicroRNAs are a group of endogenous non-coding single stranded RNAs, which play an important role in cell proliferation, differentiation, autophagy, apoptosis and inflammation. In recent years, relevant studies have found that the expression of microRNA is changed after Helicobacter pylori infection, and then regulate the biological process of host cells. This paper reviews the regulation role of microRNAs on cell biological behavior through different signal pathways after Helicobacter pylori infection.
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Affiliation(s)
- Ting Tong
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - You Zhou
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Qiaoling Huang
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Cui Xiao
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Qinqin Bai
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Bo Deng
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China
| | - Lili Chen
- Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. .,Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. .,Hengyang Engineering Technology Research Center, Hengyang, 421001, Hunan, China.
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Prasad SK, Bhat S, Shashank D, C R A, R S, Rachtanapun P, Devegowda D, Santhekadur PK, Sommano SR. Bacteria-Mediated Oncogenesis and the Underlying Molecular Intricacies: What We Know So Far. Front Oncol 2022; 12:836004. [PMID: 35480118 PMCID: PMC9036991 DOI: 10.3389/fonc.2022.836004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/22/2022] [Indexed: 01/10/2023] Open
Abstract
Cancers are known to have multifactorial etiology. Certain bacteria and viruses are proven carcinogens. Lately, there has been in-depth research investigating carcinogenic capabilities of some bacteria. Reports indicate that chronic inflammation and harmful bacterial metabolites to be strong promoters of neoplasticity. Helicobacter pylori-induced gastric adenocarcinoma is the best illustration of the chronic inflammation paradigm of oncogenesis. Chronic inflammation, which produces excessive reactive oxygen species (ROS) is hypothesized to cause cancerous cell proliferation. Other possible bacteria-dependent mechanisms and virulence factors have also been suspected of playing a vital role in the bacteria-induced-cancer(s). Numerous attempts have been made to explore and establish the possible relationship between the two. With the growing concerns on anti-microbial resistance and over-dependence of mankind on antibiotics to treat bacterial infections, it must be deemed critical to understand and identify carcinogenic bacteria, to establish their role in causing cancer.
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Affiliation(s)
- Shashanka K Prasad
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Smitha Bhat
- Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Dharini Shashank
- Department of General Surgery, Adichunchanagiri Institute of Medical Sciences, Mandya, India
| | - Akshatha C R
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Sindhu R
- Department of Microbiology, Faculty of Life Sciences, Jagadguru Sri Shivarathreeshwara (JSS) Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Pornchai Rachtanapun
- School of Agro-Industry, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai, Thailand
- Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai, Thailand
| | - Devananda Devegowda
- Centre of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Prasanna K Santhekadur
- Centre of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research (JSSAHER), Mysuru, India
| | - Sarana Rose Sommano
- Cluster of Agro Bio-Circular-Green Industry (Agro BCG), Chiang Mai University, Chiang Mai, Thailand
- Department of Plant and Soil Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai, Thailand
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9
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Wu MY, Luo YX, Jia WX, Wang DD, Sun DL, Song J, Wang J, Niu WW, Zhang XL. miRNA-320 inhibits colitis-associated colorectal cancer by regulating the IL-6R/STAT3 pathway in mice. J Gastrointest Oncol 2022; 13:695-709. [PMID: 35557592 PMCID: PMC9086045 DOI: 10.21037/jgo-22-237] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/13/2022] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). microRNA-320 (miRNA-320) promotes intestinal mucosal barrier repair in IBD and inhibits tumor progression. However, the role of miRNA-320 in the progression of CAC remains to be defined. We studied the mechanisms of miRNA-320 in the progression of CAC in mice. METHODS CAC was induced in mice (C57BL/B6) by the administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), and the mice were given a lentiviral vector (LV) overexpressing mmu-miRNA-320. The level of miRNA-320 was analyzed by quantitative real-time polymerase chain reaction (qPCR). Colonic inflammation, histological analysis, and tumorigenesis were evaluated. Ki-67 in colonic tissues was examined by immunohistochemistry. B-cell lymphoma-extra large (BCL-xl) and proliferating cell nuclear antigen (PCNA) expression was examined by Western blot. Furthermore, the proliferation, migration, and invasion of colorectal cancer (CRC) cells were evaluated. The levels of interleukin-6 receptor (IL-6R), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) were examined by Western blot and qPCR. RESULTS miRNA-320 was downregulated in CAC mice (0.57±0.13 vs. 1.00±0.12, t=-5.95, P<0.001). miRNA-320 decreased the disease activity index (DAI) scores, improved colonic inflammation, and inhibited tumor formation (tumor number: 8.00±2.90 vs. 13.67±2.73, t=-3.49, P<0.01) in mice with CAC. miRNA-320 suppressed the expression of BCL-xl, PCNA, and Ki-67 (0.38±0.07 vs. 0.69±0.08, t=-7.30, P<0.001). miRNA-320 inhibited colon cancer cell proliferation, migration, and invasion. miRNA-320 significantly inhibited the levels of IL-6R [colon tissue messenger RNA (mRNA): 4.06±1.44 vs. 10.05±1.55, t=-6.94, P<0.001], STAT3, and p-STAT3 in vivo and in vitro. Silencing IL-6R expression partially reversed the IL-6R/STAT3-suppressing and tumor-inhibiting effect of miRNA-320. CONCLUSIONS miRNA-320 inhibits tumorigenesis in mice with CAC by suppressing IL-6R/STAT3 expression, and IL-6R is a target gene of miRNA-320.
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Affiliation(s)
- Meng-Yao Wu
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Yu-Xin Luo
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Wen-Xiu Jia
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Dan-Dan Wang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Dong-Lei Sun
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Jia Song
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Jing Wang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Wei-Wei Niu
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
| | - Xiao-Lan Zhang
- Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Hebei Medical University, Shijiazhuang, China
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10
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Wang C, Hu Y, Yang H, Wang S, Zhou B, Bao Y, Huang Y, Luo Q, Yang C, Xie X, Yang S. Function of Non-coding RNA in Helicobacter pylori-Infected Gastric Cancer. Front Mol Biosci 2021; 8:649105. [PMID: 34046430 PMCID: PMC8144459 DOI: 10.3389/fmolb.2021.649105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer is a common malignant tumor of the digestive system. Its occurrence and development are the result of a combination of genetic, environmental, and microbial factors. Helicobacter pylori infection is a chronic infection that is closely related to the occurrence of gastric tumorigenesis. Non-coding RNA has been demonstrated to play a very important role in the organism, exerting a prominent role in the carcinogenesis, proliferation, apoptosis, invasion, metastasis, and chemoresistance of tumor progression. H. pylori infection affects the expression of non-coding RNA at multiple levels such as genetic polymorphisms and signaling pathways, thereby promoting or inhibiting tumor progression or chemoresistance. This paper mainly introduces the relationship between H. pylori-infected gastric cancer and non-coding RNA, providing a new perspective for gastric cancer treatment.
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Affiliation(s)
- Chao Wang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yiyang Hu
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Huan Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Sumin Wang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Bo Zhou
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yulu Bao
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Yu Huang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Qiang Luo
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Chuan Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Xia Xie
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
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11
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Palrasu M, Zaika E, El-Rifai W, Que J, Zaika AI. Role of Bacterial and Viral Pathogens in Gastric Carcinogenesis. Cancers (Basel) 2021; 13:1878. [PMID: 33919876 PMCID: PMC8070847 DOI: 10.3390/cancers13081878] [Citation(s) in RCA: 18] [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: 03/01/2021] [Revised: 04/02/2021] [Accepted: 04/11/2021] [Indexed: 01/10/2023] Open
Abstract
Gastric cancer (GC) is one of the deadliest malignancies worldwide. In contrast to many other tumor types, gastric carcinogenesis is tightly linked to infectious events. Infections with Helicobacter pylori (H. pylori) bacterium and Epstein-Barr virus (EBV) are the two most investigated risk factors for GC. These pathogens infect more than half of the world's population. Fortunately, only a small fraction of infected individuals develops GC, suggesting high complexity of tumorigenic processes in the human stomach. Recent studies suggest that the multifaceted interplay between microbial, environmental, and host genetic factors underlies gastric tumorigenesis. Many aspects of these interactions still remain unclear. In this review, we update on recent discoveries, focusing on the roles of various gastric pathogens and gastric microbiome in tumorigenesis.
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Affiliation(s)
- Manikandan Palrasu
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
| | - Elena Zaika
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
| | - Wael El-Rifai
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
- Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL 33136, USA
| | - Jianwen Que
- Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA;
| | - Alexander I. Zaika
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
- Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL 33136, USA
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12
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Riahi Rad Z, Riahi Rad Z, Goudarzi H, Goudarzi M, Mahmoudi M, Yasbolaghi Sharahi J, Hashemi A. MicroRNAs in the interaction between host-bacterial pathogens: A new perspective. J Cell Physiol 2021; 236:6249-6270. [PMID: 33599300 DOI: 10.1002/jcp.30333] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 12/17/2022]
Abstract
Gene expression regulation plays a critical role in host-pathogen interactions, and RNAs function is essential in this process. miRNAs are small noncoding, endogenous RNA fragments that affect stability and/or translation of mRNAs, act as major posttranscriptional regulators of gene expression. miRNA is involved in regulating many biological or pathological processes through targeting specific mRNAs, including development, differentiation, apoptosis, cell cycle, cytoskeleton organization, and autophagy. Deregulated microRNA expression is associated with many types of diseases, including cancers, immune disturbances, and infection. miRNAs are a vital section of the host immune response to bacterial-made infection. Bacterial pathogens suppress host miRNA expression for their benefit, promoting survival, replication, and persistence. The role played through miRNAs in interaction with host-bacterial pathogen has been extensively studied in the past 10 years, and knowledge about these staggering molecules' function can clarify the complicated and ambiguous interactions of the host-bacterial pathogen. Here, we review how pathogens prevent the host miRNA expression. We briefly discuss emerging themes in this field, including their role as biomarkers in identifying bacterial infections, as part of the gut microbiota, on host miRNA expression.
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Affiliation(s)
- Zohreh Riahi Rad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Riahi Rad
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Mahmoudi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Javad Yasbolaghi Sharahi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Hashemi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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13
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Kelley BR, Lu J, Haley KP, Gaddy JA, Johnson JG. Metal homeostasis in pathogenic Epsilonproteobacteria: mechanisms of acquisition, efflux, and regulation. Metallomics 2021; 13:mfaa002. [PMID: 33570133 PMCID: PMC8043183 DOI: 10.1093/mtomcs/mfaa002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 11/25/2020] [Accepted: 12/03/2020] [Indexed: 12/14/2022]
Abstract
Epsilonproteobacteria are a diverse class of eubacteria within the Proteobacteria phylum that includes environmental sulfur-reducing bacteria and the human pathogens, Campylobacter jejuni and Helicobacter pylori. These pathogens infect and proliferate within the gastrointestinal tracts of multiple animal hosts, including humans, and cause a variety of disease outcomes. While infection of these hosts provides nutrients for the pathogenic Epsilonproteobacteria, many hosts have evolved a variety of strategies to either sequester metals from the invading pathogen or exploit the toxicity of metals and drive their accumulation as an antimicrobial strategy. As a result, C. jejuni and H. pylori have developed mechanisms to sense changes in metal availability and regulate their physiology in order to respond to either metal limitation or accumulation. In this review, we will discuss the challenges of metal availability at the host-pathogen interface during infection with C. jejuni and H. pylori and describe what is currently known about how these organisms alter their gene expression and/or deploy bacterial virulence factors in response to these environments.
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Affiliation(s)
- Brittni R Kelley
- Department of Microbiology, University of Tennessee, Knoxville, TN, USA
| | - Jacky Lu
- Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA
| | - Kathryn P Haley
- Department of Biology, Grand Valley State University, Grand Rapids, MI, USA
| | - Jennifer A Gaddy
- Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA
- Tennessee Valley Healthcare Systems, Department of Veterans Affairs, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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14
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Mycoplasma hyopneumoniae J elicits an antioxidant response and decreases the expression of ciliary genes in infected swine epithelial cells. Sci Rep 2020; 10:13707. [PMID: 32792522 PMCID: PMC7426424 DOI: 10.1038/s41598-020-70040-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 06/22/2020] [Indexed: 12/20/2022] Open
Abstract
Mycoplasma hyopneumoniae is the most costly pathogen for swine production. Although several studies have focused on the host-bacterium association, little is known about the changes in gene expression of swine cells upon infection. To improve our understanding of this interaction, we infected swine epithelial NPTr cells with M. hyopneumoniae strain J to identify differentially expressed mRNAs and miRNAs. The levels of 1,268 genes and 170 miRNAs were significantly modified post-infection. Up-regulated mRNAs were enriched in genes related to redox homeostasis and antioxidant defense, known to be regulated by the transcription factor NRF2 in related species. Down-regulated mRNAs were enriched in genes associated with cytoskeleton and ciliary functions. Bioinformatic analyses suggested a correlation between changes in miRNA and mRNA levels, since we detected down-regulation of miRNAs predicted to target antioxidant genes and up-regulation of miRNAs targeting ciliary and cytoskeleton genes. Interestingly, most down-regulated miRNAs were detected in exosome-like vesicles suggesting that M. hyopneumoniae infection induced a modification of the composition of NPTr-released vesicles. Taken together, our data indicate that M. hyopneumoniae elicits an antioxidant response induced by NRF2 in infected cells. In addition, we propose that ciliostasis caused by this pathogen is partially explained by the down-regulation of ciliary genes.
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15
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Spitaleri A, Ghodousi A, Miotto P, Cirillo DM. Whole genome sequencing in Mycobacterium tuberculosis. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:S197. [PMID: 31656776 DOI: 10.21037/atm.2019.07.28] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Andrea Spitaleri
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Arash Ghodousi
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Miotto
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniela Maria Cirillo
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
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16
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Dastmalchi N, Safaralizadeh R, Banan Khojasteh SM. The correlation between microRNAs and Helicobacter pylori in gastric cancer. Pathog Dis 2019; 77:5539973. [DOI: 10.1093/femspd/ftz039] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 07/25/2019] [Indexed: 12/18/2022] Open
Abstract
ABSTRACT
Helicobacter pylori infection and H. pylori-related gastric inflammation can be considered as the most significant promoter of gastric cancer (GC). Recent investigations have evaluated the regulatory function of microRNAs (miRNAs) in H. pylori pathogenesis and H. pylori-related diseases, especially GC. The present study reviewed the correlation between miRNAs and H. pylori in gastrointestinal diseases. Furthermore, the current review highlighted the role of H. pylori pathogen and some H. pylori-related virulence factors in the deregulation of various miRNAs, especially oncogenic miRNAs (miRs) and their associated molecular pathways. Among the related studies, some have focused on the effects of H. pylori infection on regulatory networks of miRs, while others have highlighted the effects of alterations in the expression level of miRs in H. pylori-related diseases. The connectivity between miRNAs and H. pylori is regulated by various molecular pathways and different molecular targets of miRNAs.
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Affiliation(s)
- Narges Dastmalchi
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Reza Safaralizadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
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17
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Aguilar C, Mano M, Eulalio A. Multifaceted Roles of microRNAs in Host-Bacterial Pathogen Interaction. Microbiol Spectr 2019; 7:10.1128/microbiolspec.bai-0002-2019. [PMID: 31152522 PMCID: PMC11026079 DOI: 10.1128/microbiolspec.bai-0002-2019] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) are a well-characterized class of small noncoding RNAs that act as major posttranscriptional regulators of gene expression. Accordingly, miRNAs have been associated with a wide range of fundamental biological processes and implicated in human diseases. During the past decade, miRNAs have also been recognized for their role in the complex interplay between the host and bacterial pathogens, either as part of the host response to counteract infection or as a molecular strategy employed by bacteria to subvert host pathways for their own benefit. Importantly, the characterization of downstream miRNA targets and their underlying mechanisms of action has uncovered novel molecular factors and pathways relevant to infection. In this article, we review the current knowledge of the miRNA response to bacterial infection, focusing on different bacterial pathogens, including Salmonella enterica, Listeria monocytogenes, Mycobacterium spp., and Helicobacter pylori, among others.
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Affiliation(s)
- Carmen Aguilar
- Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
| | - Miguel Mano
- Functional Genomics and RNA-Based Therapeutics Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
| | - Ana Eulalio
- Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
- RNA & Infection Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
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18
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Zou D, Xu L, Li H, Ma Y, Gong Y, Guo T, Jing Z, Xu X, Zhang Y. Role of abnormal microRNA expression in Helicobacter pylori associated gastric cancer. Crit Rev Microbiol 2019; 45:239-251. [PMID: 30776938 DOI: 10.1080/1040841x.2019.1575793] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Epidemiological studies have shown that Helicobacter pylori (HP) infection is a risk factor for gastric cancer (GC). HP infection may induce the release of pro-inflammatory mediators, and abnormally increase the level of reactive oxygen species (ROS), nitric oxide (NO), and cytokines in mucosal epithelial cells of the stomach. However, the specific mechanism underlying the pathogenesis of HP-associated GC is still poorly understood. Recent studies have revealed that abnormal microRNA expression may affect the proliferation, differentiation, and apoptosis of mucosal epithelial cells of the stomach to further influence GC occurrence, development, and metastasis. Herein, we summarize the role of abnormal microRNAs in the regulation of HP-associated GC progression. Abnormal microRNA expression in HP-positive GC may be a biomarker for GC diagnosis, occurrence, and development as well as its targeted treatment and prognosis.
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Affiliation(s)
- Dan Zou
- a The First laboratory of cancer institute , First Hospital of China Medical University , Shenyang , China
| | - Ling Xu
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China
| | - Heming Li
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China.,c Department of Oncology , Affiliated Zhongshan Hospital of Dalian University , Dalian , China
| | - Yanju Ma
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China.,d Department of Medical Oncology , Cancer Hospital of China Medical University , Shenyang , China
| | - Yuehua Gong
- e Department of Tumor Etiology and Screening Department of Cancer Institute and General Surgery, First Hospital of China Medical University , Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department , Shenyang , China
| | - Tianshu Guo
- b Department of Medical Oncology , First Hospital of China Medical University , Shenyang , China
| | - Zhitao Jing
- f Department of Neurosurgery , First Hospital of China Medical University , Shenyang , China
| | - Xiuying Xu
- g Department of Gastroenterology , First Hospital of China Medical University , Shenyang , China
| | - Ye Zhang
- a The First laboratory of cancer institute , First Hospital of China Medical University , Shenyang , China
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19
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Mechanisms of Inflammasome Signaling, microRNA Induction and Resolution of Inflammation by Helicobacter pylori. Curr Top Microbiol Immunol 2019; 421:267-302. [PMID: 31123893 DOI: 10.1007/978-3-030-15138-6_11] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Inflammasome-controlled transcription and subsequent cleavage-mediated activation of mature IL-1β and IL-18 cytokines exemplify a crucial innate immune mechanism to combat intruding pathogens. Helicobacter pylori represents a predominant persistent infection in humans, affecting approximately half of the population worldwide, and is associated with the development of chronic gastritis, peptic ulcer disease, and gastric cancer. Studies in knockout mice have demonstrated that the pro-inflammatory cytokine IL-1β plays a central role in gastric tumorigenesis. Infection by H. pylori was recently reported to stimulate the inflammasome both in cells of the mouse and human immune systems. Using mouse models and in vitro cultured cell systems, the bacterial pathogenicity factors and molecular mechanisms of inflammasome activation have been analyzed. On the one hand, it appears that H. pylori-stimulated IL-1β production is triggered by engagement of the immune receptors TLR2 and NLRP3, and caspase-1. On the other hand, microRNA hsa-miR-223-3p is induced by the bacteria, which controls the expression of NLRP3. This regulating effect by H. pylori on microRNA expression was also described for more than 60 additionally identified microRNAs, indicating a prominent role for inflammatory and other responses. Besides TLR2, TLR9 becomes activated by H. pylori DNA and further TLR10 stimulated by the bacteria induce the secretion of IL-8 and TNF, respectively. Interestingly, TLR-dependent pathways can accelerate both pro- and anti-inflammatory responses during H. pylori infection. Balancing from a pro-inflammation to anti-inflammation phenotype results in a reduction in immune attack, allowing H. pylori to persistently colonize and to survive in the gastric niche. In this chapter, we will pinpoint the role of H. pylori in TLR- and NLRP3 inflammasome-dependent signaling together with the differential functions of pro- and anti-inflammatory cytokines. Moreover, the impact of microRNAs on H. pylori-host interaction will be discussed, and its role in resolution of infection versus chronic infection, as well as in gastric disease development.
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20
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Aguilar C, Mano M, Eulalio A. MicroRNAs at the Host-Bacteria Interface: Host Defense or Bacterial Offense. Trends Microbiol 2018; 27:206-218. [PMID: 30477908 DOI: 10.1016/j.tim.2018.10.011] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 10/17/2018] [Accepted: 10/30/2018] [Indexed: 02/07/2023]
Abstract
MicroRNAs are a class of small noncoding RNAs that act as major post-transcriptional regulators of gene expression. They are currently recognized for their important role in the intricate interaction between host and bacterial pathogens, either as part of the host immune response to neutralize infection, or as a molecular strategy employed by bacteria to hijack host pathways for their own benefit. Here, we summarize recent advances on the function of miRNAs during infection of mammalian hosts by bacterial pathogens, highlighting key cellular pathways. In addition, we discuss emerging themes in this field, including the participation of miRNAs in host-microbiota crosstalk and cell-to-cell communication.
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Affiliation(s)
- Carmen Aguilar
- Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany
| | - Miguel Mano
- Functional Genomics and RNA-based Therapeutics Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
| | - Ana Eulalio
- Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany; RNA & Infection Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
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21
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Chang WL, Yeh YC, Sheu BS. The impacts of H. pylori virulence factors on the development of gastroduodenal diseases. J Biomed Sci 2018; 25:68. [PMID: 30205817 PMCID: PMC6131906 DOI: 10.1186/s12929-018-0466-9] [Citation(s) in RCA: 127] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 08/21/2018] [Indexed: 12/12/2022] Open
Abstract
Although most H. pylori infectors are asymptomatic, some may develop serious disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and peptic ulcer disease. Epidemiological and basic studies have provided evidence that infection with H. pylori carrying specific virulence factors can lead to more severe outcome. The virulence factors that are associated with gastric adenocarcinoma development include the presence, expression intensity and types of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its translocation into the host cells, the genotypes of vacuolating cytotoxin A (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2-genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1), and expression status of outer inflammatory protein (OipA). The prevalence of these virulence factors is diverse among H. pylori isolated from different geographic areas and ethnic groups, which may explain the differences in disease incidences. For example, in East Asia where gastric cancer incidence is highest worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1 and BabA-expressing. Therefore, selection of appropriate virulence markers and testing methods are important when using them to determine risk of diseases. This review summarizes the evidences of H. pylori virulence factors in relation with gastroduodenal diseases and discusses the geographic differences and appropriate methods of analyzing these virulence markers.
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Affiliation(s)
- Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Yi-Chun Yeh
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng Li Road, Tainan, Taiwan. .,Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
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22
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Vaziri F, Tarashi S, Fateh A, Siadat SD. New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors, epigenetic modifications and non-coding RNAs. World J Clin Cases 2018; 6:64-73. [PMID: 29774218 PMCID: PMC5955730 DOI: 10.12998/wjcc.v6.i5.64] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 02/09/2018] [Accepted: 03/07/2018] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, MicroRNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.
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Affiliation(s)
- Farzam Vaziri
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Samira Tarashi
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Abolfazl Fateh
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
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23
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van Rensburg IC, du Toit L, Walzl G, du Plessis N, Loxton AG. Decreased neutrophil-associated miRNA and increased B-cell associated miRNA expression during tuberculosis. Gene 2018; 655:35-41. [PMID: 29477867 DOI: 10.1016/j.gene.2018.02.052] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 02/16/2018] [Accepted: 02/21/2018] [Indexed: 12/11/2022]
Abstract
MicroRNAs are short non-coding RNAs that regulate gene expression by binding to, and suppressing the expression of genes. Research show that microRNAs have potential to be used as biomarkers for diagnosis, treatment response and can be used for therapeutic interventions. Furthermore, microRNA expression has effects on immune cell functions, which may lead to disease. Considering the important protective role of neutrophils and B-cells during M.tb infection, we evaluated the expression of microRNAs, known to alter function of these cells, in the context of human TB. We utilised real-time PCR to evaluate the levels of microRNA transcripts in the peripheral blood of TB cases and healthy controls. We found that neutrophil-associated miR-197-3p, miR-99b-5p and miR-191-5p transcript levels were significantly lower in TB cases. Additionally, B-cell-associated miR-320a, miR-204-5p, miR331-3p and other transcript levels were higher in TB cases. The miRNAs differentially expressed in neutrophils are predominantly implicated in signalling pathways leading to cytokine productions. Here, the decreased expression in TB cases may imply a lack of suppression on signalling pathways, which may lead to increased production of pro-inflammatory cytokines such as interferon-gamma. Furthermore, the miRNAs differentially expressed in B-cells are mostly involved in the induction/suppression of apoptosis. Further functional studies are however required to elucidate the significance and functional effects of changes in the expression of these microRNAs.
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Affiliation(s)
- I C van Rensburg
- SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa
| | - L du Toit
- SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa
| | - G Walzl
- SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa
| | - N du Plessis
- SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa
| | - A G Loxton
- SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa.
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24
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Li C, Duan P, Wang J, Lu X, Cheng J. miR-320 inhibited ovarian cancer oncogenicity via targeting TWIST1 expression. Am J Transl Res 2017; 9:3705-3713. [PMID: 28861161 PMCID: PMC5575184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Accepted: 03/21/2017] [Indexed: 06/07/2023]
Abstract
Ovarian cancer is the most lethal gynecological cancer in most countries. Increasing studies have demonstrated that dysregulation of microRNAs (miRNAs) can contribute to cancer progression. In this study, we showed that miR-320 was underexpressed in ovarian cancer samples compared to their non-tumor tissues. The expression of Twist homolog 1 (TWIST1) in ovarian cancer tissues was upregulated compared with that in the non-tumorous tissues. We found that the expression of TWIST1 was inversely correlated with that of miR-320 in the ovarian cancer. Overexpression of miR-320 suppressed cell proliferation, cell cycle and invasion in ovarian cancer. We identified TWIST1 as a direct target gene of miR-320 in the ovarian cancer cell. Overexpression of TWIST1 promoted the ovarian cancer cell proliferation, cell cycle and invasion. Ectopic expression of TWIST1 restored the effects of miR-320 on cell proliferation, cell cycle and invasion. These findings revealed that miR-320 was a tumor suppressive gene that supressed cell prloferation, cycle and invasion through targeting TWIST1 in ovarian cancer.
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Affiliation(s)
- Chunyang Li
- Department of Biochemistry, School of Basic Sciences, Wenzhou Medical UniversityWenzhou 325000, Zhejiang, China
| | - Ping Duan
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027, Zhejiang, China
| | - Jianguang Wang
- Department of Biochemistry, School of Basic Sciences, Wenzhou Medical UniversityWenzhou 325000, Zhejiang, China
| | - Xiaosheng Lu
- Reproductive Health Center, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027, Zhejiang, China
| | - Jing Cheng
- Reproductive Health Center, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027, Zhejiang, China
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25
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Li B, Zhang H. Plasma microRNA-320 is a potential diagnostic and prognostic bio-marker in gastric cancer. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017; 10:7356-7361. [PMID: 31966576 PMCID: PMC6965298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 01/10/2017] [Indexed: 06/10/2023]
Abstract
OBJECTIVE MicroRNA-320 (MiR-320) had been reported to be down-regulated in several cancers. However, its clinical significance in gastric cancer remained unknown. In this study, we aimed to detect the expression of miR-320 and its clinical significance in gastric cancer. METHODS The relative expression levels of miR-320 in plasma of gastric cancer patients and healthy controls were detected using quantitative real-time polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to estimate the diagnostic value of miR-320 in gastric cancer. Moreover, its prognostic value was assessed via Kaplan-Meier and Cox regression analyses. RESULTS Compared with healthy individuals, the plasma miR-320 expression in patients with gastric cancer was significantly decreased (P<0.001). The low plasma miR-320 expression was closely associated with TNM stage and lymph node metastasis (P<0.05). Furthermore, plasma miR-320 could be used to distinguish gastric cancer patients from healthy controls with an area under the curve (AUC) of 0.861. The sensitivity and specificity were 82.4% and 75.9%, respectively. Kaplan-Meier analysis revealed that patients with high expression of miR-320 had an obviously longer overall survival than those with low miR-320 expression (log rank test, P=0.003). MiR-320 could be an independent prognostic factor for patients with gastric cancer via univariate and multivariate analyses. CONCLUSIONS Plasma miR-320 is down-regulated and correlated with the progression of gastric cancer. What's more, miR-320 may be a potential bio-marker for the diagnosis and prognosis of gastric cancer patients.
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Affiliation(s)
- Baohui Li
- Department of Medical Medicine, Cangzhou Central HospitalCangzhou, Hebei, China
| | - Hongjie Zhang
- Department of Medical Safety, Cangzhou Central HospitalCangzhou, Hebei, China
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26
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Song X, Xin N, Wang W, Zhao C. Wnt/β-catenin, an oncogenic pathway targeted by H. pylori in gastric carcinogenesis. Oncotarget 2016; 6:35579-88. [PMID: 26417932 PMCID: PMC4742126 DOI: 10.18632/oncotarget.5758] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 08/26/2015] [Indexed: 12/14/2022] Open
Abstract
A section of gastric cancers presents nuclear β-catenin accumulation correlated with H. pylori infection. H. pylori stimulate Wnt/β-catenin pathway by activating oncogenic c-Met and epidermal growth factor receptor (EGFR), or by inhibiting tumor suppressor Runx3 and Trefoil factor 1 (TFF1). H. pylori also trigger Wnt/β-catenin pathway by recruiting macrophages. Moreover, Wnt/β-catenin pathway is found involved in H. pylori-induced gastric cancer stem cell generation. Recently, by using gastroids, researchers have further revealed that H. pylori induce gastric epithelial cell proliferation through β-catenin. These findings indicate that Wnt/β-catenin is an oncogenic pathway activated by H. pylori. Therefore, this pathway is a potential therapy target for H. pylori-related gastric cancer.
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Affiliation(s)
- Xiaowen Song
- Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Na Xin
- Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Wei Wang
- Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Chenghai Zhao
- Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China
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27
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Yang Q, Zhang RW, Sui PC, He HT, Ding L. Dysregulation of non-coding RNAs in gastric cancer. World J Gastroenterol 2015; 21:10956-10981. [PMID: 26494954 PMCID: PMC4607897 DOI: 10.3748/wjg.v21.i39.10956] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 08/28/2015] [Accepted: 09/15/2015] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs (ncRNAs), primarily microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of non-coding RNAs, especially miRNAs and lncRNAs, in GC. We summarize instances of aberrant expression of the ncRNAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how ncRNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncRNAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncRNAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncRNAs have been identified as targets for the treatment of GC.
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28
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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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29
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MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma. Cancer Gene Ther 2015; 22:351-9. [PMID: 26160225 DOI: 10.1038/cgt.2015.27] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Revised: 04/07/2015] [Accepted: 04/11/2015] [Indexed: 02/06/2023]
Abstract
To investigate the biological significance of abundant microRNA-23a (miR-23a) expression in osteosarcoma and its correlation with PTEN in the pathogenesis of osteosarcoma migration and invasion. The human osteosarcoma cell lines MG63, HOS58 and SaoS-2, and the human normal osteoblasts (hFOB1.19) were grown in RPMI 1640 medium supplemented with 10% fetal bovine serum. Gene and protein levels of miR-23a and PTEN were examined to determine the molecular relationship between them in the pathogenesis of osteosarcoma. Inhibition of miR-23a effectively reduced migration and invasion of osteosarcoma cell lines. Bioinformatics and luciferase-reporter assay revealed that miR-23a specifically targeted the 3'-untranslational region of PTEN and regulated its expression. Downregulation of PTEN enhanced migration and invasion of osteosarcoma cell lines. Furthermore, in tumor tissues obtained from osteosarcoma patients, the expression of miR-23a was negatively correlated with PTEN and the high expression of miR-23a combined with low expression of PTEN might serve as a risk factor for cancer patients. Besides, miR-23a-mediated suppression of PTEN led to activation of AKT/ERK pathways and epithelial-mesenchymal transition (EMT) in osteosarcoma cells, and finally enhanced the activity of osteosarcoma cell proliferation and movement and promoted osteosarcoma xenograft tumor growth in mouse models. Our study showed that miR-23a, by downregulation of PTEN, enhanced migration and invasion in osteosarcoma cells.
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30
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Waldum HL, Hauso Ø, Sørdal ØF, Fossmark R. Gastrin May Mediate the Carcinogenic Effect of Helicobacter pylori Infection of the Stomach. Dig Dis Sci 2015; 60:1522-7. [PMID: 25480404 DOI: 10.1007/s10620-014-3468-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 11/26/2014] [Indexed: 12/14/2022]
Abstract
Gastric cancer occurs almost exclusively in patients with gastritis. Since Helicobacter pylori (Hp) was proved to cause gastritis, Hp was also expected to play a role in gastric carcinogenesis. Despite extensive studies, the mechanisms by which Hp cause gastric cancer are still poorly understood. However, there is evidence that the anatomical site of Hp infection is of major importance. Infection confined to the antral mucosa protects against gastric cancer but predisposes to duodenal ulcer, whereas Hp infection of the oxyntic mucosa increases the risk of gastric cancer. Hp infection does not predispose to cancers in the gastric cardia. In patients with atrophic gastritis of the oxyntic mucosa, the intragastric pH is elevated and the concentration of microorganisms in the stomach is increased. This does not lead to increased risk of gastric cancer at all anatomical sites. The site specificity of Hp infection in relation to cancer risk indicates that neither Hp nor the changes in gastric microflora due to gastric hypoacidity are carcinogenic per se. However, reduced gastric acidity also leads to hypergastrinemia, which stimulates the function and proliferation of enterochromaffin-like (ECL) cells located in the oxyntic mucosa. The ECL cell may be more important in human gastric carcinogenesis than previously realized, as every condition causing long-term hypergastrinemia in animals results in the development of neoplasia in the oxyntic mucosa. Patients with hypergastrinemia will far more often develop carcinomas in the gastric corpus. In conclusion, hypergastrinemia may explain the carcinogenic effect of Hp.
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Affiliation(s)
- Helge L Waldum
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Prinsesse Kristinas Gate 1, 7006, Trondheim, Norway,
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A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy. PLoS One 2015; 10:e0118745. [PMID: 25760964 PMCID: PMC4356539 DOI: 10.1371/journal.pone.0118745] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 01/12/2015] [Indexed: 12/11/2022] Open
Abstract
Purpose To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy. Methods Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence. Results Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone. Conclusion miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies.
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32
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Wan X, Ding X, Chen S, Song H, Jiang H, Fang Y, Li P, Guo J. The functional sites of miRNAs and lncRNAs in gastric carcinogenesis. Tumour Biol 2015; 36:521-32. [PMID: 25636450 PMCID: PMC4342515 DOI: 10.1007/s13277-015-3136-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Accepted: 01/19/2015] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer is one of the most common malignant diseases and has one of the highest mortality rates worldwide. Its molecular mechanisms are poorly understood. Recently, the functions of non-coding RNAs (ncRNAs) in gastric cancer have attracted wide attention. Although the expression levels of various ncRNAs are different, they may work together in a network and contribute to gastric carcinogenesis by altering the expression of oncogenes or tumor suppressor genes. They affect the cell cycle, apoptosis, motility, invasion, and metastasis. Dysregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), including miR-21, miR-106, H19, and ANRIL, directly or indirectly regulate carcinogenic factors or signaling pathways such as PTEN, CDK, caspase, E-cadherin, Akt, and P53. Greater recognition of the roles of miRNAs and lncRNAs in gastric carcinogenesis can provide new insight into the mechanisms of tumor development and identify targets for anticancer drug development.
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Affiliation(s)
- Xiangxiang Wan
- Department of Gastroenterology, Ningbo First Hospital, No. 59 Liuting Street, Ningbo, 315010, China
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Chen G, Tang Y, Wu JH, Liu FH. Role of microRNAs in diagnosis and treatment of the pathogenesis of gastric cancer. Int J Clin Exp Med 2014; 7:5947-57. [PMID: 25664140 PMCID: PMC4307587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2014] [Accepted: 12/08/2014] [Indexed: 06/04/2023]
Abstract
We aim to detect the miRNAs that are correlated with the gastric cancer cell line SGC-7901 to provide theoretical basis for clinical application. We first analyzed miRNA expression profiles of gastric cancer patients compared with normal controls by microarray analysis and validated the results by real-time qPCR. We also determined the absolute copy numbers of these three miRNAs in normal adults. The results showed that three miRNAs (miR-150, miR-23a, and miR-130a) were identified to significantly decrease in expanded 38 gastric cancer patients compared with 90 normal controls. Molecular and statistical analysis showed that the decreased miRNAs were significant in clinical analysis. Generally speaking, this finding suggest vital roles of these miRNAs in human gastric cancer genesis and as potential biomarkers in gastric cancer diagnosis.
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Affiliation(s)
- Gang Chen
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University Wuhan, China
| | - Yong Tang
- Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University Wuhan, China
| | - Jiang-Hua Wu
- Departments of Gynecological Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital Tianjin, China
| | - Feng-Hua Liu
- Departments of Gynecological Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital Tianjin, China
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34
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MicroRNAs in the interaction between host and bacterial pathogens. FEBS Lett 2014; 588:4140-7. [PMID: 25128459 DOI: 10.1016/j.febslet.2014.08.002] [Citation(s) in RCA: 132] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2014] [Revised: 08/01/2014] [Accepted: 08/04/2014] [Indexed: 02/06/2023]
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs with a central role in the post-transcriptional control of gene expression, that have been implicated in a wide-range of biological processes. Regulation of miRNA expression is increasingly recognized as a crucial part of the host response to infection by bacterial pathogens, as well as a novel molecular strategy exploited by bacteria to manipulate host cell pathways. Here, we review the current knowledge of bacterial pathogens that modulate host miRNA expression, focusing on mammalian host cells, and the implications of miRNA regulation on the outcome of infection. The emerging role of commensal bacteria, as part of the gut microbiota, on host miRNA expression in the presence or absence of bacterial pathogens is also discussed.
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35
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Zhang YM, Noto JM, Hammond CE, Barth JL, Argraves WS, Backert S, Peek RM, Smolka AJ. Helicobacter pylori-induced posttranscriptional regulation of H-K-ATPase α-subunit gene expression by miRNA. Am J Physiol Gastrointest Liver Physiol 2014; 306:G606-13. [PMID: 24503769 PMCID: PMC4116396 DOI: 10.1152/ajpgi.00333.2013] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Acute Helicobacter pylori infection of gastric epithelial cells induces CagA oncoprotein- and peptidoglycan (SLT)-dependent mobilization of NF-κB p50 homodimers that bind to H-K-ATPase α-subunit (HKα) promoter and repress HKα gene transcription. This process may facilitate gastric H. pylori colonization by induction of transient hypochlorhydria. We hypothesized that H. pylori also regulates HKα expression posttranscriptionally by miRNA interaction with HKα mRNA. In silico analysis of the HKα 3' untranslated region (UTR) identified miR-1289 as a highly conserved putative HKα-regulatory miRNA. H. pylori infection of AGS cells transfected with HKα 3' UTR-Luc reporter construct repressed luciferase activity by 70%, whereas ΔcagA or Δslt H. pylori infections partially abrogated repression. Transfection of AGS cells expressing HKα 3' UTR-Luc construct with an oligoribonucleotide mimetic of miR-1289 induced maximal repression (54%) of UTR activity within 30 min; UTR activity was unchanged by nontargeting siRNA transfection. Gastric biopsies from patients infected with cagA(+) H. pylori showed a significant increase in miR-1289 expression compared with uninfected patients or those infected with cagA(-) H. pylori. Finally, miR-1289 expression was necessary and sufficient to attenuate biopsy HKα protein expression in the absence of infection. Taken together, these data indicate that miR-1289 is upregulated by H. pylori in a CagA- and SLT-dependent manner and targets HKα 3' UTR, affecting HKα mRNA translation. The sensitivity of HKα mRNA 3' UTR to binding of miR-1289 identifies a novel regulatory mechanism of gastric acid secretion and offers new insights into mechanisms underlying transient H. pylori-induced hypochlorhydria.
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Affiliation(s)
- Yong-Mei Zhang
- 1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina;
| | - Jennifer M. Noto
- 2Vanderbilt University School of Medicine, Nashville, Tennessee;
| | - Charles E. Hammond
- 3Department of Medicine, Medical University of South Carolina, Charleston, South Carolina;
| | - Jeremy L. Barth
- 4Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina; and
| | - W. Scott Argraves
- 4Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina; and
| | - Steffen Backert
- 5Division of Microbiology, Department of Biology, Friedrich Alexander University, Erlangen, Germany
| | - Richard M. Peek
- 2Vanderbilt University School of Medicine, Nashville, Tennessee;
| | - Adam J. Smolka
- 3Department of Medicine, Medical University of South Carolina, Charleston, South Carolina;
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