|
1
|
Rai RP, Syed A, Elgorban AM, Abid I, Wong LS, Khan MS, Khatoon J, Prasad KN, Ghoshal UC. Expressions of selected microRNAs in gastric cancer patients and their association with Helicobacter pylori and its cag pathogenicity island. Microb Pathog 2025; 202:107442. [PMID: 40049249 DOI: 10.1016/j.micpath.2025.107442] [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: 07/11/2024] [Revised: 02/24/2025] [Accepted: 02/28/2025] [Indexed: 03/12/2025]
Abstract
BACKGROUND Helicobacter pylori infection and the resulting inflammation of the stomach are widely recognized as the primary risk factors for the development of gastric cancer (human health). Despite numerous attempts, the correlation between various virulence factors of H. pylori and stomach cancer remains mainly unexplained. The cag pathogenicity island (cagPAI) is a widely recognized indicator of virulence in H. pylori. MicroRNAs play crucial roles in a wide range of biological and pathological processes and dysregulated expressions of miRNAs have been detected in numerous cancer types. However, research on the correlation between H. pylori infection and its cagPAI, as well as the differential expression of microRNAs in gastric cancer, is lacking. AIM The aim of this study was to examine the differential expression of miRNAs in 80 patients with gastric cancer, specifically in connection to the presence of H. pylori and its cag pathogenicity island (cagPAI). METHODS Biopsies of 80 gastric cancer patients were collected and used for H. pylori DNA isolation and tissue miRNA isolation, and further analyzed for cagPAI and miRNA expression and their association. RESULTS Elevated levels of miR-21, miR-155, and miR-223 were detected in malignant tissues. The expression of miR-21 and miR-223 was considerably elevated in biopsies that tested positive for H. pylori, whereas the expression of miR-34a was reduced. H. pylori cagPAI samples that are functionally intact exhibit greater expression of miR-21 and miR-223 compared to cagPAI samples that are partially deleted, in both normal and malignant tissues. CONCLUSION Thus, the novelty of our study lies in its focus on the differential expression of specific miRNAs in relation to the functional integrity of the cagPAI in H. pylori-infected gastric cancer patients, offering a more detailed understanding of the interplay between H. pylori virulence factors and miRNA regulation than previous studies.
Collapse
Affiliation(s)
- Ravi Prakash Rai
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Asad Syed
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
| | - Abdallah M Elgorban
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Islem Abid
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Putra Nilai, 71800, Nilai, Negeri Sembilan, Malaysia.
| | - Mohd Sajid Khan
- Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Jahanarah Khatoon
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Kashi N Prasad
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, Lucknow, India.
| |
Collapse
|
|
2
|
Malik K, Kodgire P. Insights into the molecular mechanisms of H. pylori-associated B-cell lymphoma. Crit Rev Microbiol 2024; 50:879-895. [PMID: 38288575 DOI: 10.1080/1040841x.2024.2305439] [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: 06/18/2023] [Revised: 12/13/2023] [Accepted: 01/06/2024] [Indexed: 10/09/2024]
Abstract
Cancer research has extensively explored various factors contributing to cancer development, including chemicals, drugs, smoking, and obesity. However, the role of bacterial infections in cancer induction remains underexplored. In particular, the mechanisms underlying H. pylori-induced B-cell lymphoma, a potential consequence of bacterial infection, have received little attention. In recent years, there has been speculation about contagious agents causing persistent inflammation and encouraging B-lymphocyte transition along with lymphomagenesis. MALT lymphoma associated with chronic H. pylori infection, apart from two other central associated lymphomas - Burkitt's Lymphoma and DLBCL, is well studied. Owing to the increasing colonization of H. pylori in the host gut and its possible action in the development of B-cell lymphoma, this review aims to summarize the existing reports on different B-cell lymphomas' probable association with H. pylori infections; also emphasizing the function of the organism in lymphomagenesis; including its interaction with the host, pathogen and host-specific factors, and tumor microenvironment.
Collapse
Affiliation(s)
- Kritika Malik
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| | - Prashant Kodgire
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India
| |
Collapse
|
|
3
|
Guevara-Ramírez P, Cadena-Ullauri S, Paz-Cruz E, Tamayo-Trujillo R, Ruiz-Pozo VA, Zambrano AK. Role of the gut microbiota in hematologic cancer. Front Microbiol 2023; 14:1185787. [PMID: 37692399 PMCID: PMC10485363 DOI: 10.3389/fmicb.2023.1185787] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 08/11/2023] [Indexed: 09/12/2023] Open
Abstract
Hematologic neoplasms represent 6.5% of all cancers worldwide. They are characterized by the uncontrolled growth of hematopoietic and lymphoid cells and a decreased immune system efficacy. Pathological conditions in hematologic cancer could disrupt the balance of the gut microbiota, potentially promoting the proliferation of opportunistic pathogens. In this review, we highlight studies that analyzed and described the role of gut microbiota in different types of hematologic diseases. For instance, myeloma is often associated with Pseudomonas aeruginosa and Clostridium leptum, while in leukemias, Streptococcus is the most common genus, and Lachnospiraceae and Ruminococcaceae are less prevalent. Lymphoma exhibits a moderate reduction in microbiota diversity. Moreover, certain factors such as delivery mode, diet, and other environmental factors can alter the diversity of the microbiota, leading to dysbiosis. This dysbiosis may inhibit the immune response and increase susceptibility to cancer. A comprehensive analysis of microbiota-cancer interactions may be useful for disease management and provide valuable information on host-microbiota dynamics, as well as the possible use of microbiota as a distinguishable marker for cancer progression.
Collapse
|
|
4
|
Time-resolved RNA signatures of CD4+ T cells in Parkinson's disease. Cell Death Dis 2023; 9:18. [PMID: 36681665 PMCID: PMC9867723 DOI: 10.1038/s41420-023-01333-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/22/2023]
Abstract
Parkinson's disease (PD) emerges as a complex, multifactorial disease. While there is increasing evidence that dysregulated T cells play a central role in PD pathogenesis, elucidation of the pathomechanical changes in related signaling is still in its beginnings. We employed time-resolved RNA expression upon the activation of peripheral CD4+ T cells to track and functionally relate changes on cellular signaling in representative cases of patients at different stages of PD. While only few miRNAs showed time-course related expression changes in PD, we identified groups of genes with significantly altered expression for each different time window. Towards a further understanding of the functional consequences, we highlighted pathways with decreased or increased activity in PD, including the most prominent altered IL-17 pathway. Flow cytometric analyses showed not only an increased prevalence of Th17 cells but also a specific subtype of IL-17 producing γδ-T cells, indicating a previously unknown role in PD pathogenesis.
Collapse
|
|
5
|
Expression of Concern: Overexpression of miR-142-5p and miR-155 in Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Resistant to Helicobacter pylori Eradication. PLoS One 2023; 18:e0278797. [PMID: 36630336 PMCID: PMC9833570 DOI: 10.1371/journal.pone.0278797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
|
|
6
|
Infection and Immunity. Clin Immunol 2023. [DOI: 10.1016/b978-0-12-818006-8.00007-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
|
|
7
|
Helicobacter pylori Infection Mediates Inflammation and Tumorigenesis-Associated Genes Through miR-155-5p: An Integrative Omics and Bioinformatics-Based Investigation. Curr Microbiol 2022; 79:192. [PMID: 35551487 DOI: 10.1007/s00284-022-02880-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Accepted: 04/15/2022] [Indexed: 11/03/2022]
Abstract
Helicobacter pylori (H. pylori) is a major human pathogenic bacterium that survives in the gastric mucosa. The aim of this study is to evaluate the expression of the target gene network of miR-155-5p in H. pylori-related gastritis using a combination of public gene expression datasets and web-based platforms. To evaluate the expression of genes related to gastritis, we used two datasets from Gene Expression Omnibus (GEO) database. Then, we determined the overlaps between the predicted miR-155-5p target genes and gastritis-dysregulated GEO datasets genes; in the next step, we identified the possible miR-155-5p target-DEGs (Target-Differentially Expressed Genes). Also, we performed multiple bioinformatics analyses to identify the most important targets and downstream pathways associated with this miRNA. Using the UCSC cancer genomic browser analysis tool, we investigated the expression of hub genes in relation to gastric cancer and H. pylori infection, as well as the potential role of hub genes in gastritis, inflammation, and cancer. In this regard, 28 differentially expressed target genes of miR-155-5p were identified. Most of the captured target genes were correlated with the host immune response and inflammation. Based on the specific patterns of expression in gastritis and cancer, CD9, MST1R, and ADAM10 were candidates for the most probable targets of miR-155-5p. Although the focus of this study is primarily on bioinformatics, we think that our findings should be experimentally validated before they can be used as potential therapeutic and diagnostic tools.
Collapse
|
|
8
|
Ruan X, Zhang R, Zhu H, Ye C, Wang Z, Dong E, Li R, Cheng Z, Peng H. Research progress on epigenetics of small B-cell lymphoma. Clin Transl Oncol 2022; 24:1501-1514. [PMID: 35334078 DOI: 10.1007/s12094-022-02820-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 02/26/2022] [Indexed: 10/18/2022]
Abstract
Small B-cell lymphoma is the classification of B-cell chronic lymphoproliferative disorders that include chronic lymphocytic leukaemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. The clinical presentation is somewhat heterogeneous, and its occurrence and development mechanisms are not yet precise and may involve epigenetic changes. Epigenetic alterations mainly include DNA methylation, histone modification, and non-coding RNA, which are essential for genetic detection, early diagnosis, and assessment of treatment resistance in small B-cell lymphoma. As chronic lymphocytic leukemia/small lymphocytic lymphoma has already been reported in the literature, this article focuses on small B-cell lymphomas such as follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom macroglobulinemia. It discusses recent developments in epigenetic research to diagnose and treat this group of lymphomas. This review provides new ideas for the treatment and prognosis assessment of small B-cell lymphoma by exploring the connection between small B-cell lymphoma and epigenetics.
Collapse
Affiliation(s)
- Xueqin Ruan
- Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Engineering Research Center of Targeted Therapy for Hematopoietic Malignancies, Changsha, Hunan, China.,Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
| | - Rong Zhang
- Division of Cancer Immunotherapy, National Cancer Center Exploratory Oncology Research & Clinical Trial Center, Chiba, Japan
| | - Hongkai Zhu
- Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Engineering Research Center of Targeted Therapy for Hematopoietic Malignancies, Changsha, Hunan, China.,Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
| | - Can Ye
- Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Engineering Research Center of Targeted Therapy for Hematopoietic Malignancies, Changsha, Hunan, China.,Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
| | - Zhihua Wang
- Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Engineering Research Center of Targeted Therapy for Hematopoietic Malignancies, Changsha, Hunan, China.,Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
| | - En Dong
- Blood Center, Changsha, Hunan, China
| | - Ruijuan Li
- Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. .,Hunan Engineering Research Center of Targeted Therapy for Hematopoietic Malignancies, Changsha, Hunan, China. .,Institute of Molecular Hematology, Central South University, Changsha, Hunan, China.
| | - Zhao Cheng
- Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. .,Hunan Engineering Research Center of Targeted Therapy for Hematopoietic Malignancies, Changsha, Hunan, China. .,Institute of Molecular Hematology, Central South University, Changsha, Hunan, China.
| | - Hongling Peng
- Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.,Hunan Engineering Research Center of Targeted Therapy for Hematopoietic Malignancies, Changsha, Hunan, China.,Institute of Molecular Hematology, Central South University, Changsha, Hunan, China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| |
Collapse
|
|
9
|
Li YZ, Mou P, Shen Y, Gao LD, Chen XX, Wei RL. Effect of miR-184 and miR-205 on the tumorigenesis of conjunctival mucosa associated lymphoid tissue lymphoma through regulating RasL10B and TNFAIP8. Int J Ophthalmol 2022; 15:1-8. [PMID: 35047349 DOI: 10.18240/ijo.2022.01.01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 06/11/2021] [Indexed: 11/23/2022] Open
Abstract
AIM To explore the effect of miR-184 and miR-205 on the proliferation and metastasis of conjunctival mucosa associated lymphoid tissue (MALT) lymphoma. METHODS Tissue of tumor and adjacent normal control from 5 patients with conjunctival MALT was included. RPMI8226 cell line was selected to verify the effect of miRNAs in B cells. The function of microRNA on the RPMI8226 cell apoptosis, migration and invasion was evaluated by apoptosis assay and Transwell assay. The mRNA and protein expression were examined by quantitative RT-PCR and Western blotting. The effect of microRNA on regulation of downstream gene expression was evaluated by luciferase report assay. RESULTS A decreased level of miR-184 and miR-205 was observed in MALT lymphoma tissue. Exogenous miR-184 and miR-205 analogues promoted apoptosis, and inhibited the survival, migration, and invasion of RPMI8226 cells. miR-184 and miR-205 inhibitor reversed the process. The RNA and protein level of RasL10B and TNFAIP8 were downregulated in MALT lymphoma tissue. The exogenous of miR-184 and miR-205 promoted the expression of RasL10B and TNFAIP8. Meanwhile, inhibition of miR-184 and miR-205 repressed the expression of target gene, RasL10B and TNFAIP8. CONCLUSION miR-184 and miR-205 suppresses the tumorigenesis of conjunctival MALT lymphoma through regulating RasL10B and TNFAIP8.
Collapse
Affiliation(s)
- Yu-Zhen Li
- Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Pei Mou
- Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Ya Shen
- Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Lian-Di Gao
- Department of Nursing, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Xin-Xin Chen
- Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Rui-Li Wei
- Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| |
Collapse
|
|
10
|
Recent Advances in the Genetic of MALT Lymphomas. Cancers (Basel) 2021; 14:cancers14010176. [PMID: 35008340 PMCID: PMC8750177 DOI: 10.3390/cancers14010176] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of marginal zone lymphomas. These B-cell neoplasms may arise from many organs and usually have an indolent behavior. Recurrent chromosomal translocations and cytogenetic alterations are well characterized, some of them being associated to specific sites. Through next-generation sequencing technologies, the mutational landscape of MALT lymphomas has been explored and available data to date show that there are considerable variations in the incidence and spectrum of mutations among MALT lymphoma of different sites. Interestingly, most of these mutations affect several common pathways and some of them are potentially targetable. Gene expression profile and epigenetic studies have also added new information, potentially useful for diagnosis and treatment. This article provides a comprehensive review of the genetic landscape in MALT lymphomas. Abstract Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.
Collapse
|
|
11
|
Huang WT, Kuo SH, Kuo YC, Lin CW. miR-155-regulated mTOR and Toll-like receptor 5 in gastric diffuse large B-cell lymphoma. Cancer Med 2021; 11:555-570. [PMID: 34913612 PMCID: PMC8817081 DOI: 10.1002/cam4.4466] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/04/2021] [Accepted: 11/08/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Those in the early stage could be treated with H. pylori eradication therapy, and are classified into a sensitive group and a resistant group. METHODS Genome-wide miRNA and miRNA expression profiles were obtained from biopsy specimens of gastric DLBCL. MiRNAs and their targets as predictors of responses to H. pylori eradication therapy were identified through differential expression and pathway enrichment analysis, and further confirmed with transfection experiments in lymphoma cell lines of B-cell origin. RESULTS Genome-wide miRNA and mRNA profiles showed miR-200 was associated with the sensitive group, and that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance to H. pylori eradication therapy. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to H. pylori eradication therapy. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group and morphologic evidence of active gastritis was associated with the sensitive group. CONCLUSIONS These findings showed that activation of the miR-155-DEPTOR pathway is a marker for resistance to H. pylori eradication therapy, and that histological evaluation of active gastritis might be used as a surrogate marker to predict responses to H. pylori eradication therapy in gastric DLBCL.
Collapse
Affiliation(s)
- Wei-Ting Huang
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Sung-Hsin Kuo
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Chun Kuo
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chung-Wu Lin
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
12
|
Mamgain G, Patra P, Naithani M, Nath UK. The Role of Microbiota in the Development of Cancer Tumour Cells and Lymphoma of B and T Cells. Cureus 2021; 13:e19047. [PMID: 34853760 PMCID: PMC8608681 DOI: 10.7759/cureus.19047] [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] [Accepted: 10/25/2021] [Indexed: 11/26/2022] Open
Abstract
Human body harbours enormous numbers of microbial organisms, including bacteria, viruses, and fungi which have a momentous role in well-being and illness in humans. Immune system shelters us from pathogenic bacteria, microorganisms found in human tissues have many benefits related to the functional movement of the host by regulating important procedures such as immunity, signalling, and breakdown. Lymphocytes assume a significant part in the reaction to bacterial colonization, primarily by prompting a safe reaction to obstruction or initiation. Most immunologically occupant cells have a place with the mucosal invulnerable framework and are continually motioned by dendritic cells or other Antigen introducing cells that gather intestinal samples. Thus, Microbiome is a key contributor to developing lymphoma and specific alterations to microbiome composition could attenuate the risk. There is an indication that microbial morphology can affect and control humanoids. The difference in the composition of these microorganisms is associated with tumour development. With the increased knowledge of the connection among the human microbiome and carcinogenesis, the use of these findings to prevent, predict or diagnose of lymphomas has attracted a great attention. In this article, we explored current knowledge of various microbial ecosystems, their connection with carcinogens and the potential for useful microorganisms to control and prevent B and T cell lymphoma.
Collapse
Affiliation(s)
- Garima Mamgain
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
| | - Priyanka Patra
- Biochemistry, All India Institute of Medical Sciences, Rishikesh, IND
| | - Manisha Naithani
- Biochemistry & Advanced Center of Continuous Professional Development, All India Institute of Medical Sciences, Rishikesh, IND
| | - Uttam Kumar Nath
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
| |
Collapse
|
|
13
|
Xiao D, Zou Q, Meng L, Xu Y, Zhang H, Meng F, He L, Zhang J. Glycopeptidomics Analysis of a Cell Line Model Revealing Pathogenesis and Potential Marker Molecules for the Early Diagnosis of Gastric MALT Lymphoma. Front Cell Infect Microbiol 2021; 11:715454. [PMID: 34476221 PMCID: PMC8407071 DOI: 10.3389/fcimb.2021.715454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 07/26/2021] [Indexed: 01/17/2023] Open
Abstract
Background & Aims Gastric mucosa-associated lymphoma (GML) is a mature B cell tumor related to Helicobacter pylori (H.pylori) infection. The clinical manifestations of GML are not specific, so GML is often misdiagnosed, leading to excessive treatment. The pathogenesis of H.pylori-induced GML is not well understood and there are no molecular markers for early GML diagnosis. Methods Glycopeptidomics analyses of host cell lines (a BCG823 cell line, C823) and C823 cells infected by H. pylori isolated from patients with GML (GMALT823), gastritis (GAT823), gastric ulcer (GAU823) and gastric cancer (GAC823) were carried out to clarify the host reaction mechanism against GML and to identify potential molecular criteria for the early diagnosis of GML. Results Thirty-three samples were analyzed and approximately 2000 proteins, 200 glycoproteins and 500 glycopeptides were detected in each sample. O-glycans were the dominant glycoforms in GMALT823 cells only. Four specific glycoforms in GMALT823 cells and 2 specific glycoforms in C823 and GMALT823 cells were identified. Eight specific glycopeptides from 7 glycoproteins were found in GMALT823 cells; of these glycopeptides, 6 and 3 specific glycopeptides had high affinity for T cell epitopes and have conformational B cell epitopes, respectively. Conclusion The predominant glycoforms of host cells infected by MALT H. pylori isolates differ from others, and the glycoproteins, glycosylation sites and glycoforms might be closely related to the formation of GML, which provides new insights into the pathogenic mechanisms of H. pylori infection and suggests molecular indicators for the early diagnosis of GML.
Collapse
Affiliation(s)
- Di Xiao
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Qinghua Zou
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Le Meng
- Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University, Boston, MA, United States
| | - Yanli Xu
- Hebei University of Engineering, Affiliated Hospital, College of Medicine, Handan, China
| | - Huifang Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Fanliang Meng
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lihua He
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| |
Collapse
|
|
14
|
Biernat MM, Wróbel T. Bacterial Infection and Non-Hodgkin B-Cell Lymphoma: Interactions between Pathogen, Host and the Tumor Environment. Int J Mol Sci 2021; 22:ijms22147372. [PMID: 34298992 PMCID: PMC8305669 DOI: 10.3390/ijms22147372] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/23/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Non-Hodgkin B-cell lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms with complex etiopathology, rich symptomatology, and a variety of clinical courses, therefore requiring different therapeutic approaches. The hypothesis that an infectious agent may initiate chronic inflammation and facilitate B lymphocyte transformation and lymphogenesis has been raised in recent years. Viruses, like EBV, HTLV-1, HIV, HCV and parasites, like Plasmodium falciparum, have been linked to the development of lymphomas. The association of chronic Helicobacter pylori (H. pylori) infection with mucosa-associated lymphoid tissue (MALT) lymphoma, Borrelia burgdorferi with cutaneous MALT lymphoma and Chlamydophila psittaci with ocular adnexal MALT lymphoma is well documented. Recent studies have indicated that other infectious agents may also be relevant in B-cell lymphogenesis such as Coxiella burnettii, Campylobacter jejuni, Achromobacter xylosoxidans, and Escherichia coli. The aim of the present review is to provide a summary of the current literature on infectious bacterial agents associated with B-cell NHL and to discuss its role in lymphogenesis, taking into account the interaction between infectious agents, host factors, and the tumor environment.
Collapse
MESH Headings
- Bacterial Infections/complications
- Bacterial Infections/immunology
- Burkitt Lymphoma/complications
- Burkitt Lymphoma/microbiology
- Burkitt Lymphoma/pathology
- Carcinogenesis/genetics
- Carcinogenesis/immunology
- Carcinogenesis/metabolism
- Helicobacter Infections/complications
- Helicobacter Infections/microbiology
- Helicobacter pylori/pathogenicity
- Host-Pathogen Interactions/genetics
- Host-Pathogen Interactions/immunology
- Humans
- Lymphoma, B-Cell, Marginal Zone/complications
- Lymphoma, B-Cell, Marginal Zone/microbiology
- Lymphoma, B-Cell, Marginal Zone/pathology
- Lymphoma, Large B-Cell, Diffuse/complications
- Lymphoma, Large B-Cell, Diffuse/microbiology
- Lymphoma, Large B-Cell, Diffuse/pathology
- Tumor Microenvironment/genetics
- Tumor Microenvironment/immunology
Collapse
|
|
15
|
The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas. Biomedicines 2021; 9:biomedicines9040333. [PMID: 33806113 PMCID: PMC8064455 DOI: 10.3390/biomedicines9040333] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/14/2021] [Accepted: 03/18/2021] [Indexed: 02/07/2023] Open
Abstract
Normal B-cell development is a tightly regulated complex procedure, the deregulation of which can lead to lymphomagenesis. One common group of blood cancers is the B-cell non-Hodgkin lymphomas (NHLs), which can be categorized according to the proliferation and spread rate of cancer cells into indolent and aggressive ones. The most frequent indolent B-cell NHLs are follicular lymphoma and marginal zone lymphoma. MicroRNAs (miRNAs) are small non-coding RNAs that can greatly influence protein expression. Based on the multiple interactions among miRNAs and their targets, complex networks of gene expression regulation emerge, which normally are essential for proper B-cell development. Multiple miRNAs have been associated with B-cell lymphomas, as the deregulation of these complex networks can lead to such pathological states. The aim of the present review is to summarize the existing information regarding the multifaceted role of miRNAs in indolent B-cell NHLs, affecting the main B-cell subpopulations. We attempt to provide insight into their biological function, the complex miRNA-mRNA interactions, and their biomarker utility in these malignancies. Lastly, we address the limitations that hinder the investigation of the role of miRNAs in these lymphomas and discuss ways that these problems could be overcome in the future.
Collapse
|
|
16
|
Yang R, Liu G, Han L, Qiu Y, Wang L, Wang M. MiR-365a-3p-Mediated Regulation of HELLS/GLUT1 Axis Suppresses Aerobic Glycolysis and Gastric Cancer Growth. Front Oncol 2021; 11:616390. [PMID: 33791206 PMCID: PMC8005720 DOI: 10.3389/fonc.2021.616390] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 01/29/2021] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer (GC) is a common and invasive malignancy, which lacks effective treatment and is the third main reason of cancer death. Metabolic reprogramming is one of the main reasons that GC is difficult to treat in various environments. Particularly, abnormal glycolytic activity is the most common way of metabolism reprogramming in cancer cells. Numerous studies have shown that microRNAs play important roles in reprogramming glucose metabolism. Here, we found a microRNA-miR-365a-3p, was significantly downregulated in GC according to bioinformatics analysis. Low expression of miR-365a-3p correlated with poor prognosis of GC patients. Overexpression of miR-365a-3p in GC cells significantly inhibited cell proliferation by inducing cell cycle arrest at G1 phase. Notably, miR-365a-3p induced downregulation of HELLS through binding to its 3' untranslated region (UTR). Additionally, we found that miR-365a-3p suppressed aerobic glycolysis by inhibiting HELLS/GLUT1 axis. Lastly, we shown that overexpression of miR-365a-3p significantly inhibited tumor growth in nude mice. Conversely, Reconstituted the expression of HELLS rescued the suppressive effects of miR-365a-3p. Our data collectively indicated that miR-365a-3p functioned as a tumor suppressor in GC through downregulating HELLS. Therefore, targeting of the novel miR-365a-3p/HELLS axis could be a potentially effective therapeutic approach for GC.
Collapse
Affiliation(s)
- Rui Yang
- Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, China
| | - Gen Liu
- Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, China
| | - Limin Han
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China
- Department of Pathophysiology, Zunyi Medical University, Zunyi, China
| | - Yuheng Qiu
- Key Laboratory of Precision Oncology of Shandong Higher Education, Institute of Precision Medicine, Jining Medical University, Jining, China
| | - Lulin Wang
- Key Laboratory of Molecular Pharmacology, Liaocheng People’s Hospital, Liaocheng, China
| | - Mei Wang
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China
| |
Collapse
|
|
17
|
Amato G, Vita F, Quattrocchi P, Minciullo PL, Pioggia G, Gangemi S. Involvement of miR-142 and miR-155 in Non-Infectious Complications of CVID. Molecules 2020; 25:molecules25204760. [PMID: 33081305 PMCID: PMC7587593 DOI: 10.3390/molecules25204760] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/12/2020] [Accepted: 10/14/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Common variable immunodeficiency (CVID) is the most prevalent antibody impairment. It is characterized by failure in immunoglobulin and protective antibody generation and defined by an increased tendency toward bacterial infections, autoimmunity, and malignancy. Most CVID diagnoses do not follow a classical Mendelian pattern of inheritance. In recent years, CVID has been considered an epigenetic phenomenon in the majority of cases, overtaking previous monogenetic and/or polygenetic theories. The aim of this study was to review the role of microRNAs (miRNAs) in CVID, focusing on the involvement of the same miRNAs in various non-infectious clinical complications of CVID, mainly autoimmunity and/or cancer. MATERIALS AND METHODS A bibliographic search of the scientific literature was carried out independently by two researchers in scientific databases and search engines. The MeSH terms "microRNAs" and "common variable immunodeficiency" were used. All research articles from inception to May 2020 were considered. RESULTS The literature data showed the involvement of two miRNAs in primary immunodeficiency: miR-142 and miR-155. Both of these miRNAs have been investigated through mice models, in which miR-142 and miR-155 were deleted. These knock-out (KO) mice models showed phenotypic analogies to CVID patients with hypogammaglobulinemia, adaptive immunodeficiency, polyclonal proliferation, lung disease, and enteric inflammation. miR-142 and miR-155 have been found to be involved in the following autoimmune and neoplastic clinical complications of CVID: Gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, natural killer/Tcell lymphoma (NKTCL), and immune thrombocytopenia. CONCLUSIONS miR-142 and miR-155 deregulation leads to similar CVID phenotypesin KO mice models. Although no data are available on the involvement of these miRNAs in human CVID, their dysregulation has been detected in human CVID comorbidities. The literature data show that miRNA sequences in murine models are comparable to those in humans; therefore, miR-142 and miR-155 involvement in human CVID could be hypothesized.
Collapse
Affiliation(s)
- Giuliana Amato
- Operative Unit and School of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.A.); (F.V.); (P.Q.); (P.L.M.); (S.G.)
| | - Federica Vita
- Operative Unit and School of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.A.); (F.V.); (P.Q.); (P.L.M.); (S.G.)
| | - Paolina Quattrocchi
- Operative Unit and School of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.A.); (F.V.); (P.Q.); (P.L.M.); (S.G.)
| | - Paola Lucia Minciullo
- Operative Unit and School of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.A.); (F.V.); (P.Q.); (P.L.M.); (S.G.)
| | - Giovanni Pioggia
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy
- Correspondence:
| | - Sebastiano Gangemi
- Operative Unit and School of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (G.A.); (F.V.); (P.Q.); (P.L.M.); (S.G.)
| |
Collapse
|
|
18
|
Vlăduţ C, Ciocîrlan M, Costache RS, Jinga M, Balaban VD, Costache DO, Diculescu M. Is mucosa-associated lymphoid tissue lymphoma an infectious disease? Role of Helicobacter pylori and eradication antibiotic therapy (Review). Exp Ther Med 2020; 20:3546-3553. [PMID: 32905014 DOI: 10.3892/etm.2020.9031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 07/16/2020] [Indexed: 12/12/2022] Open
Abstract
Mucosa-associated lymphoid tissue lymphoma (MALT) is seldom considered a diagnosis hypothesis in symptomatic patients. These lymphomas present as a main risk factor for chronic gastritis due to Helicobacter pylori infection. H. pylori leads to chronic inflammation, producing lymphoid tissue in the stomach mucosa (MALT) possibly leading to malignant transformation. Even though H. pylori remains one of the most important factors in the development of MALT lymphoma, it is not mandatory in the evolution of MALT lymphoma since high-grade lymphomas present a lower prevalence of H. pylori. The prevalence of H. pylori is indirectly proportional with the progression into the gastric wall. Mucosal and submucosal MALT lymphomas have a higher prevalence of the bacteria. However, genetic factors remain a risk factor especially if eradication treatment fails. Even though a low percentage of MALT lymphomas are H. pylori-negative, some respond to antibiotic eradication treatment. This can be explained either by the immunomodulatory effect of antibiotics or by other infectious sources such as Helicobacter heilmannii and Campylobacter jejuni (small bowel lymphoma). Treatment in MALT gastric lymphoma was a breakthrough since it was the first time in oncology where tumours were cured by antibiotic therapy, leading us to wonder if MALT lymphomas are infectious disease or not?
Collapse
Affiliation(s)
- Cătălina Vlăduţ
- Department of Gastroenterology, 'Prof. Dr. Agrippa Ionescu' Clinical Emergency Hospital, 011356 Bucharest, Romania.,The Fifth Clinical Department, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Mihai Ciocîrlan
- Department of Gastroenterology, 'Prof. Dr. Agrippa Ionescu' Clinical Emergency Hospital, 011356 Bucharest, Romania.,The Fifth Clinical Department, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Raluca S Costache
- The Fifth Clinical Department, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Mariana Jinga
- The Fifth Clinical Department, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Vasile D Balaban
- The Fifth Clinical Department, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Gastroenterology, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Daniel O Costache
- Department of Research, 'Carol Davila' University Central Emergency Military Hospital, 010825 Bucharest, Romania
| | - Mircea Diculescu
- The Fifth Clinical Department, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Gastroenterology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| |
Collapse
|
|
19
|
Pathways of Gastric Carcinogenesis, Helicobacter pylori Virulence and Interactions with Antioxidant Systems, Vitamin C and Phytochemicals. Int J Mol Sci 2020; 21:ijms21176451. [PMID: 32899442 PMCID: PMC7503565 DOI: 10.3390/ijms21176451] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 08/21/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a class one carcinogen which causes chronic atrophic gastritis, gastric intestinal metaplasia, dysplasia and adenocarcinoma. The mechanisms by which H. pylori interacts with other risk and protective factors, particularly vitamin C in gastric carcinogenesis are complex. Gastric carcinogenesis includes metabolic, environmental, epigenetic, genomic, infective, inflammatory and oncogenic pathways. The molecular classification of gastric cancer subtypes has revolutionized the understanding of gastric carcinogenesis. This includes the tumour microenvironment, germline mutations, and the role of Helicobacter pylori bacteria, Epstein Barr virus and epigenetics in somatic mutations. There is evidence that ascorbic acid, phytochemicals and endogenous antioxidant systems can modify the risk of gastric cancer. Gastric juice ascorbate levels depend on dietary intake of ascorbic acid but can also be decreased by H. pylori infection, H. pylori CagA secretion, tobacco smoking, achlorhydria and chronic atrophic gastritis. Ascorbic acid may be protective against gastric cancer by its antioxidant effect in gastric cytoprotection, regenerating active vitamin E and glutathione, inhibiting endogenous N-nitrosation, reducing toxic effects of ingested nitrosodimethylamines and heterocyclic amines, and preventing H. pylori infection. The effectiveness of such cytoprotection is related to H. pylori strain virulence, particularly CagA expression. The role of vitamin C in epigenetic reprogramming in gastric cancer is still evolving. Other factors in conjunction with vitamin C also play a role in gastric carcinogenesis. Eradication of H. pylori may lead to recovery of vitamin C secretion by gastric epithelium and enable regression of premalignant gastric lesions, thereby interrupting the Correa cascade of gastric carcinogenesis.
Collapse
|
|
20
|
Bai J, Hu X, Wang R, Lü A, Sun J. MicroRNA expression profile analysis of skin immune response in crucian carp (Carassius auratus) infected by Aeromonas hydrophila. FISH & SHELLFISH IMMUNOLOGY 2020; 104:673-685. [PMID: 32505719 DOI: 10.1016/j.fsi.2020.05.077] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 05/27/2020] [Accepted: 05/28/2020] [Indexed: 06/11/2023]
Abstract
MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression in fish, but its regulatory mechanism of the skin mucosal immune response remains poorly understood. In order to investigate the immunological role of miRNAs, three sRNA libraries (mSC, mST1, mST2) from skin samples of crucian carp (Carassiusauratus) infected with Aeromonas hydrophila at three time points (0, 6 and 12 hpi) were constructed and examined using Illumina Hiseq 2000 platform. All of the identified miRNA, rRNA and tRNA were 69444 (13.39%), 29550 (5.70%) and 10704 (2.06%) in skin, respectively. At 6 and 12 hpi, 829 and 856 miRNAs were differentially expressed, respectively. Among these DEMs, 53 known and 10 novel miRNAs were all significantly differentially expressed during early infection (p < 0.01). GO and KEGG enrichment analyses revealed that 118111 target-genes were primarily involved in cellular process, metabolic process, biological regulation and stress response, such as antigen processing and presentation, complement and coagulation cascades, phagosome, MAPK, TLR, NF-κB and JAK-STAT signaling pathways. These results will help to elucidate the mechanism of miRNAs involved in the skin mucosal immune response of crucian carp against Aeromonas hydrophila infection.
Collapse
Affiliation(s)
- Jie Bai
- Tianjin Key Lab of Aqua-Ecology and Aquaculture, College of Fisheries, Tianjin Agricultural University, Tianjin, 300384, China
| | - Xiucai Hu
- Tianjin Key Lab of Aqua-Ecology and Aquaculture, College of Fisheries, Tianjin Agricultural University, Tianjin, 300384, China
| | - Ruixia Wang
- Tianjin Key Lab of Aqua-Ecology and Aquaculture, College of Fisheries, Tianjin Agricultural University, Tianjin, 300384, China
| | - Aijun Lü
- Tianjin Key Lab of Aqua-Ecology and Aquaculture, College of Fisheries, Tianjin Agricultural University, Tianjin, 300384, China.
| | - Jingfeng Sun
- Tianjin Key Lab of Aqua-Ecology and Aquaculture, College of Fisheries, Tianjin Agricultural University, Tianjin, 300384, China
| |
Collapse
|
|
21
|
Melenotte C, Mezouar S, Mège JL, Gorvel JP, Kroemer G, Raoult D. Bacterial infection and non-Hodgkin's lymphoma. Crit Rev Microbiol 2020; 46:270-287. [PMID: 32412856 DOI: 10.1080/1040841x.2020.1760786] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
One quarter of all cancers are linked to infectious diseases. The link between viral infection and cancer has been widely studied, but few reports have focused on the carcinogenic role of bacterial infection. Nonetheless, Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni are bacteria that can be associated with non-Hodgkin's lymphoma (NHL), the most common haematologic malignancy. Here, we review the evidence in favour of a link between these bacterial infections and NHL. Sero-epidemiological observation makes it possible to identify a link between H. pylori, C. burnetii, B. burgdorferi infection and NHL. Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni could be identified in NHL tissue samples at the site of chronic inflammation, where B and T lymphocytes are attracted to participate in follicle formation. Lymphoma remissions have been observed under antimicrobial therapies supporting the carcinogenic contribution of bacteria. If the theory of causality is characterized by the lack of universal criteria for establishing a causal link between two diseases, infection and lymphoma, epidemiological, clinical, and histological evidences reported here, should lead clinicians to pay attention to these infectious agents, to detect early lymphoma transformation.
Collapse
Affiliation(s)
- Cléa Melenotte
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Soraya Mezouar
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Jean-Louis Mège
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | | | - Guido Kroemer
- Cell Biology and Metabolomics platforms, Villejuif, France.,INSERM, Paris, France.,Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.,Sorbonne Paris Cité, Université Paris Descartes, Paris, France.,Université Pierre et Marie Curie, Paris, France.,Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
| | - Didier Raoult
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| |
Collapse
|
|
22
|
Elsalem L, Jum'ah AA, Alfaqih MA, Aloudat O. The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives. Clin Exp Gastroenterol 2020; 13:151-185. [PMID: 32440192 PMCID: PMC7211962 DOI: 10.2147/ceg.s243337] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.
Collapse
Affiliation(s)
- Lina Elsalem
- Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmad A Jum'ah
- Department of Conservative Dentistry, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Osama Aloudat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| |
Collapse
|
|
23
|
Zhu X, Wang X, Zhao H, Pei T, Kuang L, Wang L. BHCMDA: A New Biased Heat Conduction Based Method for Potential MiRNA-Disease Association Prediction. Front Genet 2020; 11:384. [PMID: 32425979 PMCID: PMC7212362 DOI: 10.3389/fgene.2020.00384] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 03/27/2020] [Indexed: 01/04/2023] Open
Abstract
Recent studies have indicated that microRNAs (miRNAs) are closely related to sundry human sophisticated diseases. According to the surmise that functionally similar miRNAs are more likely associated with phenotypically similar diseases, researchers have proposed a variety of valid computational models through integrating known miRNA-disease associations, disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity to discover the potential miRNA-disease relationships in biomedical researches. Taking account of the limitations of previous computational models, a new computational model based on biased heat conduction for MiRNA-Disease Association prediction (BHCMDA) was proposed in this paper, which can achieve the AUC of 0.8890 in LOOCV (Leave-One-Out Cross Validation) and the mean AUC of 0.9060, 0.8931 under the framework of twofold cross validation, fivefold cross validation, respectively. In addition, BHCMDA was further implemented to the case studies of three vital human cancers, and simulation results illustrated that there were 88% (Esophageal Neoplasms), 92% (Colonic Neoplasms) and 92% (Lymphoma) out of top 50 predicted miRNAs having been confirmed by experimental literatures, separately, which demonstrated the good performance of BHCMDA as well. Thence, BHCMDA would be a useful calculative resource for potential miRNA-disease association prediction.
Collapse
Affiliation(s)
- Xianyou Zhu
- College of Computer Science and Technology, Hengyang Normal University, Hengyang, China
| | - Xuzai Wang
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan, China
| | - Haochen Zhao
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan, China
| | - Tingrui Pei
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan, China
| | - Linai Kuang
- College of Computer Science and Technology, Hengyang Normal University, Hengyang, China.,Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan, China
| | - Lei Wang
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan, China.,College of Computer Engineering & Applied Mathematics, Changsha University, Changsha, China
| |
Collapse
|
|
24
|
Zucca E, Arcaini L, Buske C, Johnson PW, Ponzoni M, Raderer M, Ricardi U, Salar A, Stamatopoulos K, Thieblemont C, Wotherspoon A, Ladetto M. Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019; 31:17-29. [PMID: 31912792 DOI: 10.1016/j.annonc.2019.10.010] [Citation(s) in RCA: 195] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 10/07/2019] [Accepted: 10/09/2019] [Indexed: 02/08/2023] Open
Affiliation(s)
- E Zucca
- Division of Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Oncology Research, Bellinzona, Switzerland
| | - L Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - C Buske
- Comprehensive Cancer Centre, University Hospital of Ulm, Ulm, Germany
| | - P W Johnson
- Cancer Research UK Centre, Southampton General Hospital, Southampton, UK
| | - M Ponzoni
- Vita-Salute San Raffaele University and Pathology Unit, San Raffaele Scientific Institute, Milan, Italy
| | - M Raderer
- Internal Medicine I, Division of Oncology, Medical University Vienna, Vienna, Austria
| | - U Ricardi
- Department of Oncology, University of Turin, Turin, Italy
| | - A Salar
- Department of Hematology, Hospital del Mar, Barcelona, Barcelona, Spain
| | - K Stamatopoulos
- Institute of Applied Biosciences, CERTH, the Centre for Research and Technology Hellas, Thessaloniki, Greece
| | - C Thieblemont
- Department of Hematology, APHP-Saint-Louis Hospital, University Paris-Diderot, Paris, France
| | - A Wotherspoon
- Department of Histopathology, The Royal Marsden Hospital, London, UK
| | - M Ladetto
- Division of Hematology, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | | |
Collapse
|
|
25
|
Guan NN, Wang CC, Zhang L, Huang L, Li JQ, Piao X. In silico prediction of potential miRNA-disease association using an integrative bioinformatics approach based on kernel fusion. J Cell Mol Med 2019; 24:573-587. [PMID: 31747722 PMCID: PMC6933403 DOI: 10.1111/jcmm.14765] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 08/13/2019] [Accepted: 09/20/2019] [Indexed: 12/18/2022] Open
Abstract
Accumulating experimental evidence has demonstrated that microRNAs (miRNAs) have a huge impact on numerous critical biological processes and they are associated with different complex human diseases. Nevertheless, the task to predict potential miRNAs related to diseases remains difficult. In this paper, we developed a Kernel Fusion-based Regularized Least Squares for MiRNA-Disease Association prediction model (KFRLSMDA), which applied kernel fusion technique to fuse similarity matrices and then utilized regularized least squares to predict potential miRNA-disease associations. To prove the effectiveness of KFRLSMDA, we adopted leave-one-out cross-validation (LOOCV) and 5-fold cross-validation and then compared KFRLSMDA with 10 previous computational models (MaxFlow, MiRAI, MIDP, RKNNMDA, MCMDA, HGIMDA, RLSMDA, HDMP, WBSMDA and RWRMDA). Outperforming other models, KFRLSMDA achieved AUCs of 0.9246 in global LOOCV, 0.8243 in local LOOCV and average AUC of 0.9175 ± 0.0008 in 5-fold cross-validation. In addition, respectively, 96%, 100% and 90% of the top 50 potential miRNAs for breast neoplasms, colon neoplasms and oesophageal neoplasms were confirmed by experimental discoveries. We also predicted potential miRNAs related to hepatocellular cancer by removing all known related miRNAs of this cancer and 98% of the top 50 potential miRNAs were verified. Furthermore, we predicted potential miRNAs related to lymphoma using the data set in the old version of the HMDD database and 80% of the top 50 potential miRNAs were confirmed. Therefore, it can be concluded that KFRLSMDA has reliable prediction performance.
Collapse
Affiliation(s)
- Na-Na Guan
- College of Big Data Statistics, Guizhou University of Finance and Economics, Guiyang, China.,College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China
| | - Chun-Chun Wang
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China
| | - Li Zhang
- School of Information and Control Engineering, China University of Mining and Technology, Xuzhou, China
| | - Li Huang
- Academy of Arts and Design, Tsinghua University, Beijing, China.,The Future Laboratory, Tsinghua University, Beijing, China
| | - Jian-Qiang Li
- College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China
| | - Xue Piao
- School of Medical Informatics, Xuzhou Medical University, Xuzhou, China
| |
Collapse
|
|
26
|
Eslami M, Yousefi B, Kokhaei P, Arabkari V, Ghasemian A. Current information on the association of Helicobacter pylori with autophagy and gastric cancer. J Cell Physiol 2019; 234:14800-14811. [PMID: 30784066 DOI: 10.1002/jcp.28279] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 11/23/2018] [Accepted: 11/30/2018] [Indexed: 01/24/2023]
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative bacterium and causative agent of gastric cancer. H. pylori induce defective autophagy or inhibit it by means of CagA and vacuolating cytotoxin A (VacA) toxins leading to the gastric cancer induction. Impaired or defective autophagy leads to the accumulation of cytotoxic materials, such as ROS and P62 that lead to increased mutations in the DNA, genome instability, and risk of cancer formation. H. pylori CagA may inhibit autophagy through the c-Met-PI3k/Akt-mTOR signaling pathway. However, VacA induces autophagy by some signaling pathways. In the gastric epithelial cells, VacA is a necessary and sufficient factor for the creation of autophagy. While CagA is a negative regulator of this phenomenon, the elimination of this gene from H. pylori has increased autophagy and the production of inflammatory cytokines is reduced. In gastrointestinal cancers, some of the microRNAs (miRNAs) act as tumor suppressors and some other are oncogenes by regulating various genes expression. H. pylori can also modify autophagy through a mechanism that includes the function of miRNAs. In autophagy, oncogenic miRNAs inhibit activation of some tumor suppressor signaling pathways (e.g., ULK1 complex, Beclin-1 function, and Atg4 messaging), whereas tumor suppressor miRNAs can block the activation of oncogenic signaling pathways. For instance, Beclin-1 is negatively regulated by miRNA-376b (oncogenic miRNA) and miRNA-30a (tumor suppressor miRNA). Similarly, Atg4 by miRNA-376b (oncogenic miRNA) and miRNA-101 (tumor suppressor miRNA). So, this apparent paradox can be explained as that both Beclin-1 and Atg4 play different roles in a particular cell or tissue.
Collapse
Affiliation(s)
- Majid Eslami
- Department of Bacteriology and Virology, Semnan University of Medical Sciences, Semnan, Iran
| | - Bahman Yousefi
- Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Parviz Kokhaei
- Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Immune and Gene Therapy Lab, Cancer Centre Karolinska, Karolinska University Hospital, Stockholm, Sweden
| | - Vahid Arabkari
- Discipline of Pathology, Lambe Institute for Translational Research, Clinical Science Institute, School of Medicine, National University of Ireland, Galway, Ireland
| | | |
Collapse
|
|
27
|
Blosse A, Levy M, Robe C, Staedel C, Copie-Bergman C, Lehours P. Deregulation of miRNA in Helicobacter pylori-Induced Gastric MALT Lymphoma: From Mice to Human. J Clin Med 2019; 8:jcm8060845. [PMID: 31200531 PMCID: PMC6616415 DOI: 10.3390/jcm8060845] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 06/05/2019] [Accepted: 06/06/2019] [Indexed: 12/12/2022] Open
Abstract
Gastric MALT lymphoma (GML) is directly caused by Helicobacter pylori infection but occurs only in a small number of infected subjects. Mechanisms underlying the initiation and progression of GML remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs that are now considered as major players in inflammation and carcinogenesis, acting as oncogenes or tumor suppressors. Previous laboratory studies have shown in a GML mouse model that overexpression of a distinct set of five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) could play a critical role in the pathogenesis of GML. Our goal was to compare the miRNA expression profile obtained in the GML mouse model to that in human GML (11 cases of GML compared to 17 cases of gastritis control population). RTqPCR on the five dysregulated miRNAs in the GML mouse model and PCR array followed by RTqPCR confirmation showed that four miRNAs were up-regulated (miR-150, miR-155, miR-196a, miR-138) and two miRNAs down-regulated (miR-153, miR-7) in the stomachs of GML patients vs. gastritis control population. The analysis of their validated targets allowed us to postulate that these miRNAs (except miR-138) could act synergistically in a common signaling cascade promoting lymphomagenesis and could be involved in the pathogenesis of GML.
Collapse
Affiliation(s)
- Alice Blosse
- INSERM, Université Bordeaux, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, 33000 Bordeaux, France.
| | - Michael Levy
- EC2M3: Department of Academic Research (EA7375), Université Paris Est Créteil (UPEC), Val de Marne, 94000 Créteil, France.
- Department of Gastroenterology, Henri Mondor Hospital, APHP, 94000 Créteil, France.
| | | | - Cathy Staedel
- INSERM U1212, ARNA Laboratory, Université de Bordeaux, 33000 Bordeaux, France.
| | - Christiane Copie-Bergman
- Department of Pathology, Henri Mondor Hospital, APHP, INSERM U955, Equipe 9, Université Paris-Est, 94000 Créteil, France.
| | - Philippe Lehours
- INSERM, Université Bordeaux, UMR1053 Bordeaux Research in Translational Oncology, BaRITOn, 33000 Bordeaux, France.
- French National Reference Center for Campylobacters & Helicobacters, 33000 Bordeaux, France.
| |
Collapse
|
|
28
|
Ou Y, Ren H, Zhao R, Song L, Liu Z, Xu W, Liu Y, Wang S. Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR-155/KLF4 signaling pathway. Mol Carcinog 2019; 58:1427-1437. [PMID: 31162747 DOI: 10.1002/mc.23025] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 03/31/2019] [Accepted: 04/08/2019] [Indexed: 12/18/2022]
Abstract
The Helicobacter pylori (H. pylori) cytotoxin-associated gene A (CagA) and Krüppel-like transcription factor (KLF4) were both closely associated with the development and progression of gastric cancer (GC). However, the nature of the interactions between CagA and KLF4 in GC development has not been elucidated. Therefore, we focused on the CagA-mediated promotion of the malignant transformation of gastric epithelial cells. Herein, we first examined the expression of KLF4 in both human cancer and paracarcinoma tissues with or without H. pylori infection and found that KLF4 expression was significantly decreased in H. pylori-positive GC cells compared with the H. pylori-negative GC cells. Further functional studies revealed that the increased expression of CagA could suppress KLF4 expression and promote the malignant transformation of normal epithelial cells. Subsequently, we found that CagA could upregulate miR-155 and further restrict the expression of downstream KLF4. More importantly, the overexpression of miR-155 in GES-1 promoted epithelial-mesenchymal transition and eventually facilitated tumor growth in vivo. Overall, the identification of the CagA/miR-155/KLF4 signaling pathway provided a new insight into the development and treatment of GC.
Collapse
Affiliation(s)
- Yang Ou
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Haifeng Ren
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Rongrong Zhao
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Le Song
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Zhengxia Liu
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Wenting Xu
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Yakun Liu
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| | - Siying Wang
- Department of physiopathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, PR China
| |
Collapse
|
|
29
|
Yan J, Yang B, Lin S, Xing R, Lu Y. Downregulation of miR-142-5p promotes tumor metastasis through directly regulating CYR61 expression in gastric cancer. Gastric Cancer 2019; 22:302-313. [PMID: 30178386 DOI: 10.1007/s10120-018-0872-4] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Accepted: 08/18/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recurrence is a primary cause of gastric cancer (GC)-related deaths. We reported previously that low expression of miR-142-5p could predict recurrence in GC. The present study aimed to investigate the function and mechanism of miR-142-5p in metastasis of GC. METHODS MiR-142-5p expression was detected in 101 GC samples by qRT-PCR. Its clinical significance was statistically analyzed. The roles of miR-142-5p and its candidate target gene CYR61 in metastasis were determined both in vivo and in vitro. RESULTS MiR-142-5p downregulation was significantly associated with the recurrence (P = 0.031) and poor prognosis of GC (P = 0.043). MiR-142-5p inhibited cancer cell migration and invasion both in vitro and in vivo. CYR61 was identified as a novel direct target of miR-142-5p by bioinformatics analysis of target prediction and luciferase reporter assay. The re-expression and knockdown of CYR61 could, respectively, rescue the effects induced by miR-142-5p overexpression and knockdown. MiR-142-5p attenuated GC cell migration and invasion, at least partially, by inactivation of the canonical Wnt/β-catenin signaling pathway through CYR61. CONCLUSIONS The newly identified miR-142-5p-CYR61-Wnt/β-catenin axis partially illustrates the molecular mechanism of GC recurrence and represents a novel prognosis biomarker for GC.
Collapse
Affiliation(s)
- Jing Yan
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Bing Yang
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Shuye Lin
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Rui Xing
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Youyong Lu
- Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| |
Collapse
|
|
30
|
Saito Y, Konno K, Sato M, Nakano M, Kato Y, Saito H, Serizawa H. Vonoprazan-Based Third-Line Therapy Has a Higher Eradication Rate against Sitafloxacin-Resistant Helicobacter pylori. Cancers (Basel) 2019; 11:cancers11010116. [PMID: 30669474 PMCID: PMC6356600 DOI: 10.3390/cancers11010116] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 01/11/2019] [Accepted: 01/17/2019] [Indexed: 12/14/2022] Open
Abstract
Eradication of Helicobacter pylori (H. pylori) is an effective strategy for preventing various gastrointestinal diseases such as gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. However, the eradication success rate is decreasing because of a recent increase in drug-resistant strains of H. pylori. Here, we evaluated the success rate of eradication therapy with vonoprazan (VPZ), a new potassium-competitive acid blocker, against drug-resistant H. pylori. In total, 793 patients who received H. pylori eradication therapy were investigated retrospectively. All underwent esomeprazole (EPZ)-based triple therapy (n = 386) or VPZ-based triple therapy (n = 407) for first-, second- and third-line H. pylori eradication for 7 days. The overall success rates of first- and third-line H. pylori eradication were significantly higher for VPZ-based triple therapy (88.4% and 93.0%, respectively, per protocol (PP)) than for EPZ-based triple therapy (69.5% and 56.5%, respectively, PP). Moreover, the success rates of first- and third-line eradication of clarithromycin (CLR)- and sitafloxacin (STFX)-resistant H. pylori were significantly higher for VPZ-based triple therapy (72.0% and 91.7%, PP) than for EPZ-based triple therapy (38.5% and 20.0%, PP). In addition, patient age did not affect the eradication rate of VPZ-based first-line therapy, whereas the success rate of EPZ-based therapy was lower in patients under 65 years of age. Our results clearly demonstrated that VPZ-based therapy achieved a higher eradication rate even against CLR- and STFX-resistant H. pylori, and that patient age did not affect the eradication rate of VPZ-based therapy. These findings suggest that dual therapy using VPZ and amoxicillin may be sufficient for standard H. pylori eradication, and may thus also be beneficial for avoiding antibiotic misuse.
Collapse
Affiliation(s)
- Yoshimasa Saito
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
- Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
| | - Kaho Konno
- Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
| | - Moeka Sato
- Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
| | - Masaru Nakano
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
| | - Yukako Kato
- Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
| | - Hidetsugu Saito
- Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
| | - Hiroshi Serizawa
- Healthcare Department, Hitachi Systems, Ltd. 1-2-1 Osaki, Shinagawa-ku, Tokyo 141-8672, Japan.
| |
Collapse
|
|
31
|
Marcelis L, Tousseyn T, Sagaert X. MALT Lymphoma as a Model of Chronic Inflammation-Induced Gastric Tumor Development. Curr Top Microbiol Immunol 2019; 421:77-106. [PMID: 31123886 DOI: 10.1007/978-3-030-15138-6_4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Mucosa-associated lymphoid tissue (MALT) lymphoma, or extranodal marginal zone lymphoma of MALT, is an indolent B-cell non-Hodgkin lymphoma linked with preexisting chronic inflammation. The stomach is the most commonly affected organ and the MALT lymphoma pathogenesis is clearly associated with Helicobacter pylori gastroduodenitis. Inflammation induces the lymphoid infiltrates in extranodal sites, where the lymphoma then subsequently develops. Genetic aberrations arise through the release of reactive oxygen species (ROS), H. pylori-induced endonucleases, and other effects. The involvement of nuclear factor kappa B (NF-κB) pathway activation, a critical regulator of pro-inflammatory responses, further highlights the role of inflammation in gastric MALT lymphoma. The NF-κB pathway regulates key elements of normal lymphocyte function, including the transcription of proliferation-promoting and anti-apoptotic genes. Aberrant constitutive activation of NF-κB signaling can lead to autoimmunity and malignancy. NF-κB pathway activation can happen through both the canonical and non-canonical pathways and can be caused by multiple genetic aberrations such as t(11;18)(q12;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) translocations, chronic inflammation and even directly by H. pylori-associated mechanisms. Gastric MALT lymphoma is considered one of the best models of how inflammation initiates genetic events that lead to oncogenesis, determines tumor biology, dictates clinical behavior and leads to viable therapeutic targets. The purpose of this review is to present gastric MALT lymphoma as an outstanding example of the close pathogenetic link between chronic inflammation and tumor development and to describe how this information can be integrated into daily clinical practice.
Collapse
Affiliation(s)
- Lukas Marcelis
- Translational Cell and Tissue Research Lab, Department of Imaging and Pathology, KU Leuven, Louvain, Belgium
- , O&N IV Herestraat 49 - bus 7003 24, 3000, Louvain, Belgium
| | - Thomas Tousseyn
- Translational Cell and Tissue Research Lab, Department of Imaging and Pathology, KU Leuven, Louvain, Belgium
- Department of Pathology, UZ Leuven, University Hospitals, Louvain, Belgium
- , O&N IV Herestraat 49 - bus 7003 24, 3000, Louvain, Belgium
| | - Xavier Sagaert
- Translational Cell and Tissue Research Lab, Department of Imaging and Pathology, KU Leuven, Louvain, Belgium.
- Department of Pathology, UZ Leuven, University Hospitals, Louvain, Belgium.
- , O&N IV Herestraat 49 - bus 7003 24, 3000, Louvain, Belgium.
| |
Collapse
|
|
32
|
miRNAs reshape immunity and inflammatory responses in bacterial infection. Signal Transduct Target Ther 2018; 3:14. [PMID: 29844933 PMCID: PMC5968033 DOI: 10.1038/s41392-018-0006-9] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 11/20/2017] [Accepted: 12/10/2017] [Indexed: 12/15/2022] Open
Abstract
Pathogenic bacteria cause various infections worldwide, especially in immunocompromised and other susceptible individuals, and are also associated with high infant mortality rates in developing countries. MicroRNAs (miRNAs), small non-coding RNAs with evolutionarily conserved sequences, are expressed in various tissues and cells that play key part in various physiological and pathologic processes. Increasing evidence implies roles for miRNAs in bacterial infectious diseases by modulating inflammatory responses, cell penetration, tissue remodeling, and innate and adaptive immunity. This review highlights some recent intriguing findings, ranging from the correlation between aberrant expression of miRNAs with bacterial infection progression to their profound impact on host immune responses. Harnessing of dysregulated miRNAs in bacterial infection may be an approach to improving the diagnosis, prevention and therapy of infectious diseases. Changes in production of tiny cellular RNAs in response to bacterial infection could guide the development of better diagnostics and therapies. MicroRNAs regulate other genes by binding to messenger RNA strands and controlling their translation into proteins. Xikun Zhou, Min Wu and colleagues of the University of North Dakota have now reviewed current knowledge about how microRNA levels shift during infection with various bacterial pathogens. These microRNAs can modulate the immune response as well as pathways that influence metabolic activity and cell survival. Increasing studies have indicated that shifts in microRNA levels in response to different infections could provide a potential bacterial ‘fingerprint’ for achieving accurate diagnosis. With deeper insight into how different microRNAs influence infection, it might one day day become possible to target these molecules with ‘antisense’ or ‘agonist’ drugs that modulate their activity.
Collapse
|
|
33
|
MicroRNA Signatures in Diagnosis and Prognosis of Cutaneous T-Cell Lymphoma. J Invest Dermatol 2018; 138:2024-2032. [PMID: 29559342 DOI: 10.1016/j.jid.2018.03.1500] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 02/22/2018] [Accepted: 03/08/2018] [Indexed: 12/24/2022]
Abstract
Cutaneous T cell lymphoma (CTCL) can have clinical and histological features resembling benign inflammatory dermatosis and can be difficult to diagnose. Very limited biomarkers are available for CTCL prognosis. We aimed to identify microRNA (miR) signatures to facilitate diagnostic and prognostic evaluations of CTCL. A cross-platform miR microarray identified 10 miRs that were differentially expressed between CTCL and benign inflammatory dermatosis patients. Subsequent reverse transcription polymerase chain reaction validation was used to generate a 5-miR-based diagnosing classifier, which showed high diagnostic accuracy in CTCL (area under the curve = 0.985 and 0.956 for training and testing set, respectively). Association between miR expressions and patient prognosis was studied. miR-155 and miR-200b were significantly associated with overall survival in CTCL patients, outperformed Ki-67. miR expressions were combined with Ki-67 to create a classifier for 5-year overall survival in CTCL patients. Our work provided miR signatures to facilitate CTCL diagnosis and prognosis with satisfying accuracy.
Collapse
|
|
34
|
Zhang X, Ji W, Huang R, Li L, Wang X, Li L, Fu X, Sun Z, Li Z, Chen Q, Zhang M. MicroRNA-155 is a potential molecular marker of natural killer/T-cell lymphoma. Oncotarget 2018; 7:53808-53819. [PMID: 27462776 PMCID: PMC5288223 DOI: 10.18632/oncotarget.10780] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 07/09/2016] [Indexed: 12/22/2022] Open
Abstract
Natural killer/T-cell lymphoma (NKTCL) is characterized by its highly aggressive nature and rapid progression. MicroRNAs (miRNAs) play key roles in the development of NKTCL. We utilized next-generation Solexa high-throughput sequencing to compare miRNA expression in the SNK-6 and YTS NKTCL cell lines with expression in normal NK cells. We found that 195 miRNAs were upregulated in the SNK-6 cells and 286 miRNAs were upregulated in the YTS cells. Based on those results, we selected six miRNAs, including miRNA-155, and confirmed their expression using real-time polymerase chain reaction. Expression of miRNA-155 was higher in SNK-6 and YKS cells than in normal NK cells. We next determined the levels of miRNA-155 in the serum of healthy individuals and NKTCL patients, and correlated its expression with clinical parameters and inflammatory factors detected using enzyme-linked immunoabsorbent assays. Levels of miRNA-155 were higher in NKTCL patients' serum than in serum from healthy individuals. miRNA-155 expression was higher in patients with stable or progressive disease (SD+PD) than in those with partial or complete remission (PR+CR). While further studies are needed to clarify the underlying molecular mechanisms, it appears miRNA-155 may be a molecular marker of NKTCL.
Collapse
Affiliation(s)
- Xudong Zhang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Weiguo Ji
- Department of Oncology, Third Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou 450008, China
| | - Ruixia Huang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Lifeng Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Xinhua Wang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Ling Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Xiaorui Fu
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Zhenchang Sun
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Zhaoming Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Qingjiang Chen
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| | - Mingzhi Zhang
- Department of Oncology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450008, China
| |
Collapse
|
|
35
|
LRSSLMDA: Laplacian Regularized Sparse Subspace Learning for MiRNA-Disease Association prediction. PLoS Comput Biol 2017; 13:e1005912. [PMID: 29253885 PMCID: PMC5749861 DOI: 10.1371/journal.pcbi.1005912] [Citation(s) in RCA: 186] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 01/02/2018] [Accepted: 12/01/2017] [Indexed: 12/17/2022] Open
Abstract
Predicting novel microRNA (miRNA)-disease associations is clinically significant due to miRNAs’ potential roles of diagnostic biomarkers and therapeutic targets for various human diseases. Previous studies have demonstrated the viability of utilizing different types of biological data to computationally infer new disease-related miRNAs. Yet researchers face the challenge of how to effectively integrate diverse datasets and make reliable predictions. In this study, we presented a computational model named Laplacian Regularized Sparse Subspace Learning for MiRNA-Disease Association prediction (LRSSLMDA), which projected miRNAs/diseases’ statistical feature profile and graph theoretical feature profile to a common subspace. It used Laplacian regularization to preserve the local structures of the training data and a L1-norm constraint to select important miRNA/disease features for prediction. The strength of dimensionality reduction enabled the model to be easily extended to much higher dimensional datasets than those exploited in this study. Experimental results showed that LRSSLMDA outperformed ten previous models: the AUC of 0.9178 in global leave-one-out cross validation (LOOCV) and the AUC of 0.8418 in local LOOCV indicated the model’s superior prediction accuracy; and the average AUC of 0.9181+/-0.0004 in 5-fold cross validation justified its accuracy and stability. In addition, three types of case studies further demonstrated its predictive power. Potential miRNAs related to Colon Neoplasms, Lymphoma, Kidney Neoplasms, Esophageal Neoplasms and Breast Neoplasms were predicted by LRSSLMDA. Respectively, 98%, 88%, 96%, 98% and 98% out of the top 50 predictions were validated by experimental evidences. Therefore, we conclude that LRSSLMDA would be a valuable computational tool for miRNA-disease association prediction. Discovering miRNA-disease associations promotes the understanding towards the molecular mechanisms of various human diseases at the miRNA level, and contributes to the development of diagnostic biomarkers and treatment tools for diseases. Computational models can make the discovery more efficient and experiments more productive. LRSSLMDA was proposed to computationally infer potential miRNA-disease associations via adopting sparse subspace learning with Laplacian regularization on the known miRNA-disease association network and the informative feature profiles extracted from the integrated miRNA/disease similarity networks. Experimental results in global and local leave-one-out cross validation and 5-fold cross validation showed a superior prediction performance of LRSSLMDA over previous models. Moreover, three types of case studies on five important human diseases were carried out to further demonstrate the model’s predictive power: respectively, 98%, 88%, 96%, 98% and 98% out of the top 50 predicted miRNAs were confirmed by experimental literatures. So, we believe that LRSSLMDA could make reliable predictions and might guide future experimental studies on miRNA-disease associations.
Collapse
|
|
36
|
Kuriyama K, Enomoto Y, Suzuki R, Watanuki J, Hosoi H, Yamashita Y, Murata S, Mushino T, Tamura S, Hanaoka N, Dyer M, Siebert R, Kiyonari H, Nakakuma H, Kitamura T, Sonoki T. Enforced expression of MIR142, a target of chromosome translocation in human B-cell tumors, results in B-cell depletion. Int J Hematol 2017; 107:345-354. [PMID: 29071477 DOI: 10.1007/s12185-017-2360-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 10/16/2017] [Accepted: 10/18/2017] [Indexed: 12/22/2022]
Abstract
MicroRNA142 (MIR142) is a target of chromosome translocations and mutations in human B-cell lymphomas. We analyzed an aggressive B-cell lymphoma carrying t(8;17)(q24;q22) and t(6;14)(p21;q32), and sought to explore the role(s) of MIR142 in lymphomagenesis. t(8;17)(q24;q22) involved MYC on 8q24 and pri-MIR142 on 17q22. MYC was activated by a promoter substitution by t(8;17)(q24;q22). t(8;17)(q24;q22) was an additional event after t(6;14) (p21;q32), which caused the over-expression of CCND3. Southern blot analyses revealed that the MIR142 locus was deleted from the affected allele, whereas Northern analyses showed over-expression of MIR142 in tumor cells. Although previous studies reported an over-expression of mutations in MIR142 in B-cell lymphomas, limited information is available on the functions of MIR142 in lymphomagenesis. Therefore, we generated bone marrow transplantation (BMT) and transgenic (Eμ/mir142) mice, which showed enforced expression in hematopoietic progenitor cells and B cells, respectively. BMT mice showed decreased numbers of all lineage-positive cells, particularly B cells, in peripheral blood. Eμ/mir142 mice showed decreased numbers of IgM-positive splenocytes, and exhibited altered B-cell phenotypic changes induced by lipopolysaccharide. Our results suggest that over-expression of MIR142 alters B-cell differentiation, implying multi-step lymphomagenesis together with MYC activation and CCND3 over-expression.
Collapse
Affiliation(s)
- Kodai Kuriyama
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Yutaka Enomoto
- Division of Cellular Therapy and Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.,Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan
| | - Ritsuro Suzuki
- Hematology and Oncology, Shimane Medical University, Shimane, Japan
| | - Jyuri Watanuki
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Hiroki Hosoi
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Yusuke Yamashita
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Shogo Murata
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Toshiki Mushino
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Shinobu Tamura
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Nobuyoshi Hanaoka
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Martin Dyer
- Department of Cancer Studies and Molecular Medicine, Leicester Medical School, University of Leicester, Leicester, UK
| | - Reiner Siebert
- Institute of Human Genetics, Christian Albrechts University Kiel, Kiel, Germany.,Institute of Human Genetics, University of Ulm and University of Ulm Medical Center, Ulm, Germany
| | - Hiroshi Kiyonari
- Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Kobe, Japan.,Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Japan
| | - Hideki Nakakuma
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan
| | - Toshio Kitamura
- Division of Cellular Therapy and Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Takashi Sonoki
- Hematology/Oncology, Wakayama Medical University, 811-1 Kimi-idera, Wakayama, 641-8510, Japan.
| |
Collapse
|
|
37
|
Omori M, Maeda S, Igarashi H, Ohno K, Sakai K, Yonezawa T, Horigome A, Odamaki T, Matsuki N. Fecal microbiome in dogs with inflammatory bowel disease and intestinal lymphoma. J Vet Med Sci 2017; 79:1840-1847. [PMID: 28993566 PMCID: PMC5709562 DOI: 10.1292/jvms.17-0045] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Although alteration of commensal microbiota is associated with chronic gastrointestinal (GI) diseases such as inflammatory bowel disease (IBD) in dogs, the microbiota composition in intestinal lymphoma, an important differential
diagnosis of canine IBD, has not been investigated. The objective of this study was to compare the fecal microbiota in dogs with IBD, dogs with intestinal lymphoma, and healthy dogs. Eight dogs with IBD, eight dogs with intestinal
lymphoma, and fifteen healthy dogs were included in the study. Fecal samples were analyzed by 16S rRNA gene next-generation sequencing. Rarefaction analysis failed to reveal any difference in bacterial diversity among healthy dogs
and diseased dogs. Based on PCoA plots of unweighted UniFrac distances, the bacterial composition in dogs with intestinal lymphoma was different from those observed in dogs with IBD and healthy dogs. When compared with healthy
dogs, intestinal lymphoma subjects showed significant increases in organisms belonging to the Eubacteriaceae family. The proportion of the family Paraprevotellaceae and the genus Porphyromonas was significantly
higher in dogs with IBD compared to healthy dogs. These observations suggest that dysbiosis is associated with intestinal lymphoma as well as IBD in dogs.
Collapse
Affiliation(s)
- Marie Omori
- Department of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Shingo Maeda
- Department of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Hirotaka Igarashi
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Koichi Ohno
- Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Kosei Sakai
- Department of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Tomohiro Yonezawa
- Department of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| | - Ayako Horigome
- Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa 252-8583, Japan
| | - Toshitaka Odamaki
- Food Science and Technology Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa 252-8583, Japan
| | - Naoaki Matsuki
- Department of Veterinary Clinical Pathobiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
| |
Collapse
|
|
38
|
Solé C, Larrea E, Di Pinto G, Tellaetxe M, Lawrie CH. miRNAs in B-cell lymphoma: Molecular mechanisms and biomarker potential. Cancer Lett 2017; 405:79-89. [DOI: 10.1016/j.canlet.2017.07.020] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 07/06/2017] [Accepted: 07/14/2017] [Indexed: 12/16/2022]
|
|
39
|
Keck J, Gupta R, Christenson LK, Arulanandam BP. MicroRNA mediated regulation of immunity against gram-negative bacteria. Int Rev Immunol 2017; 36:287-299. [PMID: 28800263 PMCID: PMC6904929 DOI: 10.1080/08830185.2017.1347649] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Evidence over the last couple decades has comprehensively established that short, highly conserved, non-coding RNA species called microRNA (miRNA) exhibit the ability to regulate expression and function of host genes at the messenger RNA (mRNA) level. MicroRNAs play key regulatory roles in immune cell development, differentiation, and protective function. Intrinsic host immune response to invading pathogens rely on intricate orchestrated events in the development of innate and adaptive arms of immunity. We discuss the involvement of miRNAs in regulating these processes against gram negative pathogens in this review.
Collapse
Affiliation(s)
- Jonathon Keck
- South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249
| | - Rishein Gupta
- South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249
| | - Lane K. Christenson
- Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160
| | - Bernard P. Arulanandam
- South Texas Center for Emerging Infectious Diseases and Center of Excellence in Infection Genomics, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249
| |
Collapse
|
|
40
|
Li Z, Abdalla BA, Zheng M, He X, Cai B, Han P, Ouyang H, Chen B, Nie Q, Zhang X. Systematic transcriptome-wide analysis of mRNA-miRNA interactions reveals the involvement of miR-142-5p and its target (FOXO3) in skeletal muscle growth in chickens. Mol Genet Genomics 2017; 293:69-80. [PMID: 28866851 DOI: 10.1007/s00438-017-1364-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 08/29/2017] [Indexed: 11/29/2022]
Abstract
The goal of this study was to perform a systematic transcriptome-wide analysis of mRNA-miRNA interactions and to identify candidates involved in the interplay between miRNAs and mRNAs that regulate chicken muscle growth. We used our previously published mRNA (GSE72424) and miRNA (GSE62971) deep sequencing data from two-tailed samples [i.e., the highest (h) and lowest (l) body weights] of Recessive White Rock (WRR) and Xinghua (XH) chickens to conduct integrative analyses of the miRNA-mRNA interactions involved in chicken skeletal muscle growth. A total of 162, 15, 173, and 27 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of the WRRh vs. XHh, WRRh vs. WRRl, WRRl vs. XHl, and XHh vs. XHl comparisons, respectively. Ingenuity Pathway Analysis revealed that gene networks identified for the WRRh vs. XHh contrast were associated with developmental disorders. Importantly, the WRRh vs. XHh contrast miRNA-mRNA network was enriched in IGF-1 signaling pathway genes, including FOXO3. A dual-luciferase reporter assay showed that FOXO3 was a target of miR-142-5p. Furthermore, miR-142-5p overexpression significantly decreased FOXO3 mRNA levels and promoted the expression of growth-related genes. These data demonstrated that miR-142-5p targets FOXO3 and promotes growth-related gene expression and regulates skeletal muscle growth in chicken. Comprehensive analysis facilitated the identification of miRNAs and target genes that might contribute to the regulation of skeletal muscle development. Our results provide new clues for understanding the molecular basis of chicken growth.
Collapse
Affiliation(s)
- Zhenhui Li
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Bahareldin Ali Abdalla
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Ming Zheng
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Xiaomei He
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Bolin Cai
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Peigong Han
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Hongjia Ouyang
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Biao Chen
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| | - Qinghua Nie
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China. .,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China.
| | - Xiquan Zhang
- Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Wushan Street, Tianhe District, Guangzhou, 510642, Guangdong, China.,Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, Guangdong, China
| |
Collapse
|
|
41
|
Suppression of microRNA-142-5p attenuates hypoxia-induced apoptosis through targeting SIRT7. Biomed Pharmacother 2017; 94:394-401. [PMID: 28772218 DOI: 10.1016/j.biopha.2017.07.083] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 07/10/2017] [Accepted: 07/19/2017] [Indexed: 12/21/2022] Open
Abstract
Increasing study has suggested that microRNAs (miRNAs) are pivotal regulators in regulating hypoxia-induced injury. miR-142-5p has been suggested as a critical regulator for cellular survival. However, the role of miR-142-5p in regulating hypoxia-induced injury remains unknown. In this study, we aimed to investigate the mechanistic roles of miR-142-5p in regulating cell survival during hypoxia treatment using H9C2 cardiomyoblasts and primary cardiomyocytes. We showed that miR-142-5p expression level was significantly repressed by hypoxia treatment. Overexpression of miR-142-5p during hypoxia induced extensive cell injury and apoptosis whereas suppression of miR-142-5p significantly promoted cell viability and attenuated cell apoptosis with hypoxia treatment. Sirtuin7 (SIRT7) was identified as a direct target gene of miR-142-5p by bioinformatics analysis and dual-luciferase reporter assays. Overexpression of miR-142-5p significantly decreased SIRT7 expression, while suppression of miR-142-5p increased SIRT7 expression. Furthermore, overexpression of SIRT7 protected H9C2 cardiomyoblasts and primary cardiomyocytes against hypoxia-induced injury and apoptosis. The silencing of SIRT7 markedly abrogated the protective effect induced by miR-142-5p suppression. Taken together, these results suggest that downregulation of miR-142-5p alleviates hypoxia-induced injury through upregulation of SIRT7. Our study suggests miR-142-5p/SIRT7 as potential therapeutic targets for ischemic heart disease.
Collapse
|
|
42
|
Jayaraman M, Radhakrishnan R, Mathews CA, Yan M, Husain S, Moxley KM, Song YS, Dhanasekaran DN. Identification of novel diagnostic and prognostic miRNA signatures in endometrial cancer. Genes Cancer 2017; 8:566-576. [PMID: 28740575 PMCID: PMC5511890 DOI: 10.18632/genesandcancer.144] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
With the goal of identifying diagnostic and prognostic biomarkers in endometrial cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84-cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96-5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR-374a and let-7 family of miRNAs in endometrial cancer. We validated the dysregulated expression of the identified miRNAs in a panel of endometrial cancer cell-lines. Immunohistochemical analysis of the tissue micro array derived from these patients established the functional correlation between the decreased expression of tumor suppressive miRNAs and their target oncogenes: ERBB2, EGFR, EPHA2, BAX, GNA12, GNA13, and JUN. Comparative analysis of the samples from the patients with extended progression-free survival (PFS) ( > 21 months) versus the patients with the PFS of < 21 months indicated increased expression of tumor suppressive miR-142-3p, miR-142-5p, and miR-15a-5p in samples from extended PFS patients. In addition to defining a specific set of miRNAs and their target genes as potential diagnostic biomarkers, our studies have identified tumor suppressive miR-142 cluster and miR-15a as predictors of favorable prognosis for therapy response in endometrial cancer.
Collapse
Affiliation(s)
- Muralidharan Jayaraman
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | | | - Cara A Mathews
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Mingda Yan
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Sanam Husain
- Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Katherine M Moxley
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Yong Sang Song
- Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, S. Korea
| | - Danny N Dhanasekaran
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| |
Collapse
|
|
43
|
Floch P, Izotte J, Guillemaud J, Sifré E, Costet P, Rousseau B, Laur AM, Giese A, Korolik V, Mégraud F, Dubus P, Hahne M, Lehours P. A New Animal Model of Gastric Lymphomagenesis. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 187:1473-1484. [DOI: 10.1016/j.ajpath.2017.03.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 02/27/2017] [Accepted: 03/09/2017] [Indexed: 12/29/2022]
|
|
44
|
Liu S, Xiao Z, Ai F, Liu F, Chen X, Cao K, Ren W, Zhang X, Shu P, Zhang D. miR-142-5p promotes development of colorectal cancer through targeting SDHB and facilitating generation of aerobic glycolysis. Biomed Pharmacother 2017. [PMID: 28622713 DOI: 10.1016/j.biopha.2017.05.134] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Aberrant expression of miRNAs contributes to the development of human malignancies. A recent study revealed that miR-142-5p is increased in the serum of colorectal cancer (CRC) patients compared to health people. Using starBase v2.0, we found that succinate dehydrogenase-B (SDHB) is a potential target of miR-142-5p, while SDHB is negatively correlated to cancer development through regulating energetic metabolism. Based on these information, this study further examined the expression profiles of miR-142-5p and SDHB in CRC tissues and cell lines using PCR and Western blotting. Transfection experiment and luciferase assay were performed to identify relationship between miR-142-5p and SDHB. Oxygen intake, glucose consumption and production of lactic acid were used to evaluate the influence on energetic metabolism. CRC growth and proliferation were assessed by in vitro and in vivo studies. Results showed that miR-142-5p was up-regulated in CRC, but SDHB was down-regulated. SDHB was confirmed as a target of miR-142-5p, and decreased SDHB in CRC was result from the abnormal up-regulation of miR-142-5p. Lose of SDHB by miR-142-5p inhibited oxygen intake by CRC cells, but increased glucose consumption and lactate production. These suggest miR-142-5p up-regulation in CRC probably facilitates generation of aerobic glycolysis by reducing SDHB. miR-142-5p promoted proliferation and colony formation of CRC, but inhibited apoptosis. SDHB overexpression abrogated these effect of miR-142-5p, which indicates that SDHB depletion mediates tumor-promoting actions of miR-142-5p. This study added novel insight into the CRC development regulated by miR-142-5p. It may be a promising therapy target in the future molecular therapy.
Collapse
Affiliation(s)
- Shaojun Liu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China
| | - Zhiming Xiao
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China
| | - Feiyan Ai
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410013 Hunan, China
| | - Fen Liu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410013 Hunan, China
| | - Xiong Chen
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China
| | - Ke Cao
- Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan, China
| | - Weiguo Ren
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410013 Hunan, China
| | - Xuemei Zhang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410013 Hunan, China
| | - Peng Shu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410013 Hunan, China
| | - Decai Zhang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha 410013 Hunan, China.
| |
Collapse
|
|
45
|
Floch P, Capdevielle C, Staedel C, Izotte J, Sifré E, Laur AM, Giese A, Korolik V, Dubus P, Mégraud F, Lehours P. Deregulation of MicroRNAs in Gastric Lymphomagenesis Induced in the d3Tx Mouse Model of Helicobacter pylori Infection. Front Cell Infect Microbiol 2017; 7:185. [PMID: 28560185 PMCID: PMC5432547 DOI: 10.3389/fcimb.2017.00185] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 04/27/2017] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori infection is considered as an excellent model of chronic inflammation-induced tumor development. Our project focuses on gastric MALT lymphoma (GML) related to H. pylori infection and mediated by the chronic inflammatory process initiated by the infection. Recently, microRNAs (miRNAs) have emerged as a new class of gene regulators, which play key roles in inflammation and carcinogenesis acting as oncogenes or tumor suppressors. Their precise characterization in the development of inflammation and their contribution in regulating host cells responses to infection by H. pylori have been little explored. Our goal was to analyze the changes in miRNAs in a GML mouse model using BALB/c mice thymectomized at day 3 post-birth (d3Tx model) and to clarify their implication in GML pathogenesis. PCR array followed by RT-qPCR identified five miRNAs (miR-21a, miR-135b, miR-142a, miR-150, miR-155) overexpressed in the stomachs of GML-developing d3Tx mice infected by H. pylori. The analysis of their putative targets allowed us to identify TP53INP1, an anti-proliferative and pro-apoptotic protein, as a common target of 4 of the 5 up-regulated miRNAs. We postulate that these miRNAs may act in synergy to promote the development of GML. miR-142a was also overexpressed in mouse sera samples and therefore could serve as a diagnostic marker. In situ hybridization on gastric samples with miR-142a revealed a global up-regulation of this miRNA by the tumor microenvironment at the lymphoma stage. Dysregulation of miR-21a, miR-135b, miR-142a, miR-150, miR-155 could play a critical role in the pathogenesis of GML and might offer potential applications as therapeutic targets and novel biomarkers for this disease.
Collapse
Affiliation(s)
- Pauline Floch
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Caroline Capdevielle
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Cathy Staedel
- ARNA Laboratory, Institut National de la Santé et de la Recherche Médicale U1212, Université de BordeauxBordeaux, France
| | - Julien Izotte
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Elodie Sifré
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Amandine M Laur
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Alban Giese
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Victoria Korolik
- Institute for Glycomics, Griffith UniversityGold Coast, QLD, Australia
| | - Pierre Dubus
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Francis Mégraud
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| | - Philippe Lehours
- UMR1053 Bordeaux Research in Translational Oncology, Institut National de la Santé et de la Recherche Médicale, University of BordeauxBordeaux, France
| |
Collapse
|
|
46
|
Wang N, Zhang L, Lu Y, Zhang M, Zhang Z, Wang K, Lv J. Down-regulation of microRNA-142-5p attenuates oxygen-glucose deprivation and reoxygenation-induced neuron injury through up-regulating Nrf2/ARE signaling pathway. Biomed Pharmacother 2017; 89:1187-1195. [PMID: 28320085 DOI: 10.1016/j.biopha.2017.03.011] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 02/26/2017] [Accepted: 03/05/2017] [Indexed: 01/01/2023] Open
Abstract
MicroRNAs (miRNAs) play vital roles in regulating neuron survival during cerebral ischemia/reperfusion injury. miR-142-5p is reported to be an important regulator of cellular survival. However, little is known about the role of miR-142-5p in regulating neuron survival during cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the precise function and mechanism of miR-142-5p in the regulation of neuron ischemia/reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neurons in vitro. We found that miR-142-5p was induced in hippocampal neurons with OGD/R treatment. The inhibition of miR-142-5p attenuated OGD/R-induced cell injury and oxidative stress, whereas the overexpression of miR-142-5p aggravated them. Nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as a target gene of miR-142-5p. Moreover, miR-142-5p regulated Nrf2 expression and downstream signaling. Knockdown of Nrf2 abolished the protective effects of miR-142-5p suppression. In addition, we showed an inverse correlation relationship between miR-142-5p and Nrf2 in an in vivo model of middle cerebral artery occlusion in rats. Taken together, these results suggest that miR-142-5p contributes to OGD/R-induced cell injury and the down-regulation of miR-142-5p attenuates OGD/R-induced neuron injury through promoting Nrf2 expression. Our study provides a novel insight into understanding the molecular pathogenesis of cerebral ischemia/reperfusion injury and indicates a potential therapeutic target for the treatment of cerebral ischemia/reperfusion injury.
Collapse
Affiliation(s)
- Ning Wang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Lingmin Zhang
- Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Yang Lu
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Mingxin Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of The Fourth Military Medical University, Xi'an 710038, China
| | - Zhenni Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Kui Wang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Jianrui Lv
- Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
| |
Collapse
|
|
47
|
Fernández C, Bellosillo B, Ferraro M, Seoane A, Sánchez-González B, Pairet S, Pons A, Barranco L, Vela MC, Gimeno E, Colomo L, Besses C, Navarro A, Salar A. MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis. Cancer Genomics Proteomics 2017; 14:75-82. [PMID: 28031239 DOI: 10.21873/cgp.20020] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 12/09/2016] [Accepted: 12/15/2016] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated. MATERIALS AND METHODS We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes. Then, significantly deregulated miRNAs were individually assessed by real-time PCR in a validation series of 16 gastric MALT lymphomas and 12 chronic gastritis. RESULTS Gastric MALT lymphoma is characterized by a specific miRNA expression profile. Among the differentially expressed miRNAs, a significant overexpression of miR-142-3p and miR-155 and down-regulation of miR-203 was observed in gastric MALT lymphoma when compared to chronic gastritis. CONCLUSION miR-142-3p, miR-155 and miR-203 expression levels might be helpful biomarkers for the differential diagnosis between gastric MALT lymphomas and chronic gastritis.
Collapse
Affiliation(s)
- Concepción Fernández
- Pathology Department, Hospital del Mar, Barcelona, Spain.,IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.,Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Beatriz Bellosillo
- Pathology Department, Hospital del Mar, Barcelona, Spain .,IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.,Universitat Pompeu Fabra, Barcelona, Spain
| | - Mariana Ferraro
- Universitat Autònoma de Barcelona, Barcelona, Spain.,Hematology Department, Hospital del Mar, Barcelona, Spain
| | - Agustín Seoane
- Digestive Department, Hospital del Mar, Barcelona, Spain
| | - Blanca Sánchez-González
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.,Hematology Department, Hospital del Mar, Barcelona, Spain
| | - Silvia Pairet
- Pathology Department, Hospital del Mar, Barcelona, Spain.,IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Aina Pons
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Luis Barranco
- Digestive Department, Hospital del Mar, Barcelona, Spain
| | | | - Eva Gimeno
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.,Hematology Department, Hospital del Mar, Barcelona, Spain
| | - Lluís Colomo
- Pathology Department, Hospital del Mar, Barcelona, Spain
| | - Carles Besses
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.,Hematology Department, Hospital del Mar, Barcelona, Spain
| | - Alfons Navarro
- Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - Antonio Salar
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.,Universitat Autònoma de Barcelona, Barcelona, Spain.,Hematology Department, Hospital del Mar, Barcelona, Spain
| |
Collapse
|
|
48
|
Lou K, Chen N, Li Z, Zhang B, Wang X, Chen Y, Xu H, Wang D, Wang H. MicroRNA-142-5p Overexpression Inhibits Cell Growth and Induces Apoptosis by Regulating FOXO in Hepatocellular Carcinoma Cells. Oncol Res 2017; 25:65-73. [PMID: 28081734 PMCID: PMC7840786 DOI: 10.3727/096504016x14719078133366] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Abnormal expression of microRNA (miR)-142-5p has been reported in hepatocellular carcinoma (HCC). However, little information is available regarding the functional role of miR-142-5p in HCC. We aimed to explore the effects of miR-142-5p aberrant expression on HCC cell growth and cell apoptosis, as well as the underlying mechanism. Human HCC cell lines HepG2 and SMMC-7721 cells were transfected with miR-142-5p mimic, inhibitor, or a corresponding negative control. Cell viability, cell cycle distribution, and cell apoptosis were then analyzed. In addition, protein expression of Forkhead box, class O (FOXO) 1 and 3, a Bcl-2-interacting mediator of cell death (Bim), procaspase 3, and activated caspase 3 was measured. After transfection with miR-142-5p inhibitor, FOXO1 and FOXO3 were overexpressed, and then the cell viability and cell apoptosis were determined again. The relative cell viability in both HepG2 and SMMC-7721 cells was significantly reduced by miR-142-5p overexpression (p < 0.05). miR-142-5p overexpression displayed a significant blockage at the G1/S transition and significantly increased the percentages of G0/G1 phase. Moreover, the results showed that miR-142-5p overexpression significantly induced cell apoptosis and statistically elevated the protein expression levels of FOXO1, FOXO3, Bim, procaspase 3, and activated caspase 3. However, the cells transfected with miR-142-5p inhibitor showed contrary results. Additionally, the effects of miR-142-5p inhibitor on cell viability and apoptosis were reversed by overexpression of FOXO. In conclusion, our results suggest that miR-142-5p overexpression shows an important protective role in HCC by inhibiting cell growth and inducing apoptosis. These effects might be by regulating FOXO expression in HCC cells.
Collapse
Affiliation(s)
- Kexin Lou
- *Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Ning Chen
- †Department of Gynecology and Obstetrics, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Zhihong Li
- *Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Bei Zhang
- †Department of Gynecology and Obstetrics, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Xiuli Wang
- ‡Central Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Ye Chen
- *Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Haining Xu
- *Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Dongwei Wang
- *Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| | - Hao Wang
- *Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
| |
Collapse
|
|
49
|
Verma P, Pandey RK, Prajapati P, Prajapati VK. Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Human Infectious Diseases. Front Microbiol 2016; 7:1274. [PMID: 27574520 PMCID: PMC4983550 DOI: 10.3389/fmicb.2016.01274] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 08/02/2016] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are evolutionary conserved, small non-coding RNA with size ranging from 19 to 24 nucleotides. They endogenously regulate the gene expression at the post transcriptional level either through translation repression or mRNA degradation. MiRNAs have shown the potential to be used as a biomarker for the diagnosis, prognosis, and therapy of infectious diseases. Many miRNAs have shown significantly altered expression during infection. The altered expression of miRNA level in an infected human can be identified by the use of advanced diagnostic tools. In this review, we have highlighted the use of miRNA as an emerging tool for the identification of the human infectious disease. Till date, several miRNAs have been reported as a molecular biomarker in infectious diseases, such as miRNA-150 and miRNA-146b-5p in human immunodeficiency virus (HIV); miRNA-122, miRNA-21, and miRNA-34a in hepatitis; miRNA-361-5p and miRNA-29c in tuberculosis; miRNA-16 and miRNA-451 in malaria and miRNA-181 in Helicobacter pylori infection. The diagnosis of infection with the help of a biomarker is a non-invasive tool that has shown to have a key role in early diagnosis of infection. The discovery of circulating miRNA in the blood of infected patients has the potential to become a powerful non-invasive biomarker in coming future.
Collapse
Affiliation(s)
- Parmila Verma
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer India
| | - Rajan K Pandey
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer India
| | | | - Vijay K Prajapati
- Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer India
| |
Collapse
|
|
50
|
Iwasaki K, Yamamoto T, Inanaga Y, Hiramitsu T, Miwa Y, Murotani K, Narumi S, Watarai Y, Katayama A, Uchida K, Kobayashi T. MiR-142-5p and miR-486-5p as biomarkers for early detection of chronic antibody-mediated rejection in kidney transplantation. Biomarkers 2016; 22:45-54. [PMID: 27323802 DOI: 10.1080/1354750x.2016.1204000] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p < 0.01) underexpressed in patients with DSA. After DSA production, miR-486-5p and its target PTEN/foxO3 mRNA were significantly overexpressed (p < 0.01) and underexpressed (p < 0.01), respectively, in patients with biopsy-proven CAMR, compared with non-CAMR. Our studies suggest that miRNA expression patterns may serve as noninvasive diagnostic biomarkers to evaluate immune response and kidney allograft status.
Collapse
Affiliation(s)
- Kenta Iwasaki
- a Department of Kidney Disease and Transplant Immunology , Aichi Medical University , Nagakute , Japan
| | - Takayuki Yamamoto
- b Department of Transplant Surgery , Nagoya Daini Red Cross Hospital , Nagoya , Japan
| | - Yukiko Inanaga
- c Department of Surgery II , Nagoya University School of Medicine , Nagoya , Japan
| | - Takahisa Hiramitsu
- b Department of Transplant Surgery , Nagoya Daini Red Cross Hospital , Nagoya , Japan
| | - Yuko Miwa
- c Department of Surgery II , Nagoya University School of Medicine , Nagoya , Japan
| | - Kenta Murotani
- d Department of Center for Clinical Research , Aichi Medical University , Nagakute , Japan
| | - Shuji Narumi
- b Department of Transplant Surgery , Nagoya Daini Red Cross Hospital , Nagoya , Japan
| | - Yoshihiko Watarai
- b Department of Transplant Surgery , Nagoya Daini Red Cross Hospital , Nagoya , Japan
| | - Akio Katayama
- e Department of Transplant Surgery , Masuko Memorial Hospital , Nagoya , Japan
| | - Kazuharu Uchida
- a Department of Kidney Disease and Transplant Immunology , Aichi Medical University , Nagakute , Japan.,f Department of Transplant Surgery , Aichi Medical University , Nagakute , Japan
| | - Takaaki Kobayashi
- f Department of Transplant Surgery , Aichi Medical University , Nagakute , Japan
| |
Collapse
|