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Soni DK, Cabrera-Luque J, Kar S, Ahmed A, Sen C, Devaney J, Biswas R. Suppression of miR-155 Attenuates Lung Cytokine Storm Induced by SARS-CoV-2 Infection. J Interferon Cytokine Res 2025; 45:150-161. [PMID: 39950973 DOI: 10.1089/jir.2024.0253] [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] [Indexed: 04/02/2025] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a deadly human viral disease with a high rate of infection, morbidity, and mortality. Although vaccines and antiviral treatments are available, hospitalizations remain steady, and concerns about long-term consequences persist. Therefore, there is a great urgency to develop novel therapies. Here, we analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Endogenous microRNAs (miRNAs, miRs) are key molecules in preventing viral entry and replication while building an antiviral cellular defense. Our study reveals that miR-155 expression is elevated in patients with COVID-19. Using a mouse model transgenic for human angiotensin-converting enzyme receptor 2, we evaluated the potential of anti-miR-155 therapy. Treating SARS-CoV-2-infected mice with anti-miR-155 significantly reduced miR-155 expression, improved survival, and slightly increased body weight. Notably, these mice showed altered expression of cytokines in the lungs. These findings suggest anti-miR-155 could be a promising therapy to mitigate the cytokine storm and long-lasting symptoms induced by SARS-CoV-2 infection, improving public health outcomes and enhancing global pandemic preparedness.
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Affiliation(s)
- Dharmendra Kumar Soni
- Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | | | | | - Anwar Ahmed
- Department of Preventive Medicine and Biostatistics, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Chaitali Sen
- Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | | | - Roopa Biswas
- Department of Anatomy, Physiology and Genetics, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
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Wang S, Chen L, Wu Z, Zou Y, Li Y, He X, Zhang Y, Huang B. MiR-362-3p mediates IFNα-induced antiviral viability against Enterovirus 71 (EV71). NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04062-6. [PMID: 40137969 DOI: 10.1007/s00210-025-04062-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 03/13/2025] [Indexed: 03/29/2025]
Abstract
Enteroviruses, which belong to the Picornaviridae family, include species that infect humans and Interferon Alpha (IFNα) is commonly used against Enterovirus 71 (EV71) infections. This study investigated the role of IFNα-induced miR-362-3p expression in the defense against EV71EV71. Differential analysis identified up-regulated miRNAs following IFNα treatment. RD cells were used to assess EV71proliferation, while HMC3 cells were employed to evaluate the effects of IFNα and EV71 on miR-362-3p expression. Antiviral activity was assessed by modulating miR-362-3p levels. Compared to the NC mimic group, miR-362-3p in miR-362-3p mimic and IFNα treatment groups was increased; cell viability was enhanced; -lgTCID50 was reduced, and the replication of EV71 was inhibited. Further, VP1 mRNA and protein expression declined significantly in miR-362-3p mimic group vs NC mimic while they were notably elevated in the miR-362-3p inhibitor group vs NC inhibitor. IFNα treatment could induce miR-362-3p production and enhanced cell viability in HMC3 cells. Besides, when compared with the miR-362-3p mimic group, IFNα combined with miR-362-3p mimic group reduced -lgTCID50 and significantly decreased the expression of VP1 mRNA and protein. Conclusion: The inhibition of EV71-infected HMC3 cell replication was related to the upregulation of miR-362-3p induced by IFNα, which in turn enhanced antiviral viability.
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Affiliation(s)
- San Wang
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China
| | - Lan Chen
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China
| | - Zongtao Wu
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China
| | - Yingbo Zou
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China
| | - Yunrong Li
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China
| | - Xiang He
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China
| | - Yusong Zhang
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China
| | - Bo Huang
- Department of Pediatrics, The Third Affiliated Hospital of Zunyi Medical University, the First People'S Hospital of Zunyi), Guizhou, 563099, China.
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Bahojb Mahdavi SZ, Jebelli A, Aghbash PS, Baradaran B, Amini M, Oroojalian F, Pouladi N, Baghi HB, de la Guardia M, Mokhtarzadeh AA. A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection. Med Res Rev 2025; 45:349-425. [PMID: 39185567 PMCID: PMC11796338 DOI: 10.1002/med.22073] [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: 11/06/2021] [Revised: 04/11/2023] [Accepted: 08/04/2024] [Indexed: 08/27/2024]
Abstract
Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.
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Affiliation(s)
- Seyedeh Zahra Bahojb Mahdavi
- Department of Biology, Faculty of Basic SciencesAzarbaijan Shahid Madani UniversityTabrizIran
- Immunology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Asiyeh Jebelli
- Department of Biological Science, Faculty of Basic ScienceHigher Education Institute of Rab‐RashidTabrizIran
- Tuberculosis and Lung Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | | | - Behzad Baradaran
- Immunology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Mohammad Amini
- Immunology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Fatemeh Oroojalian
- Department of Advanced Sciences and Technologies in Medicine, School of MedicineNorth Khorasan University of Medical SciencesBojnurdIran
| | - Nasser Pouladi
- Department of Biology, Faculty of Basic SciencesAzarbaijan Shahid Madani UniversityTabrizIran
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Lin T, Meegaskumbura M. Fish MicroRNA Responses to Thermal Stress: Insights and Implications for Aquaculture and Conservation Amid Global Warming. Animals (Basel) 2025; 15:624. [PMID: 40075907 PMCID: PMC11898199 DOI: 10.3390/ani15050624] [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: 01/13/2025] [Revised: 02/11/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
In the context of global warming, heat tolerance is becoming a crucial physiological trait influencing fish species' distribution and survival. While our understanding of fish heat tolerance and stress has expanded from behavioral studies to transcriptomic analyses, knowledge at the transcriptomic level is still limited. Recently, the highly conserved microRNAs (miRNAs) have provided new insights into the molecular mechanisms of heat stress in fish. This review systematically examines current research across three main reference databases to elucidate the universal responses and mechanisms of fish miRNAs under heat stress. Our initial screening of 569 articles identified 13 target papers for comprehensive analysis. Among these, at least 214 differentially expressed miRNAs (DEMs) were found, with 15 DEMs appearing in at least two studies (12 were upregulated and 13 were downregulated). The 15 recurrent DEMs were analyzed using DIANA mirPath v.3 and the microT-CDS v5.0 database to identify potential target genes. The results suggest that multiple miRNAs target various genes, forming a complex network that regulates glucose and energy metabolism, maintains homeostasis, and modulates inflammation and immune responses. Significantly, miR-1, miR-122, let-7a, and miR-30b were consistently differentially expressed in multiple studies, indicating their potential relevance in heat stress responses. However, these miRNAs should not be considered definitive biomarkers without further validation. Future research should focus on experimentally confirming their regulatory roles through functional assays, conducting transcriptomic comparisons across different species, and performing target validation studies. These miRNAs, conserved across species, could be valuable for monitoring wild fish health, enhancing aquaculture breeding, and guiding conservation strategies. However, the specific regulatory mechanisms of these miRNAs need clarification to confirm their reliability as biomarkers for thermal stress.
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Affiliation(s)
| | - Madhava Meegaskumbura
- Guangxi Key Laboratory of Forest Ecology and Conservation, College of Forestry, Guangxi University, Nanning 530004, China
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He Y, Hu Y, Ye T. Small G Protein Regulates Virus Infection via MiRNA and Autophagy in Shrimp. Biomolecules 2025; 15:277. [PMID: 40001579 PMCID: PMC11853464 DOI: 10.3390/biom15020277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 02/10/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Recently, there has been a burgeoning scholarly interest in elucidating the functional significance and regulatory mechanisms underlying the involvement of small G proteins, such as Rab, in the antiviral immune response of crustaceans. Rab is a member of the small G protein family and plays a crucial role in the transport of cell membranes within eukaryotic cells. It is involved in the movement of cell membranes both within the cell and on its surface, aiding in the entry of effector proteins into specific membrane subregions. While previous research has highlighted the importance of Rab in phagosome formation and maturation, as well as the clearance of innate immune pathogens by phagocytes, its role in regulating autophagy and the antiviral mechanism remains unclear. This study focused on Rab10 and its role in the autophagy pathway within shrimp, as it pertains to defending against viral infections. MiRNA targeting Rab10 was analyzed and verified by bioinformatic methods. It was found that inhibition of miR-2c could enhance the shrimp's ability to combat viral infections. This discovery suggests a potential new strategy for screening antiviral drugs. In summation, this investigation augments our comprehension of the antiviral mechanism associated with Rab10, illuminating its significance in the antiviral immune response of shrimp.
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Affiliation(s)
- Yaodong He
- School of Fisheries, Zhejiang Ocean University, Zhoushan 316022, China;
| | - Yiqi Hu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China;
| | - Ting Ye
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China;
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Yıldırım Ç, Yay F, İmre A, Soysal O, Yıldırım HÇ. CXCL10, SCGN, and H2BC5 as Potential Key Genes Regulated by HCV Infection. Genes (Basel) 2024; 15:1502. [PMID: 39766770 PMCID: PMC11675613 DOI: 10.3390/genes15121502] [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: 10/11/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 01/03/2025] Open
Abstract
Introduction: Hepatitis C infections are the main causes of fatal clinical conditions such as cirrhosis and HCC development, and biomarkers are needed to predict the development of these complications. Therefore, it is important to first determine which genes are deregulated in HCV-cells compared to healthy individuals. In our study, we aimed to identify the genes that are commonly upregulated or downregulated in HCV-infected cells using two different databases. Material and Method: In this study, differentially expressed genes (DEGs) that were commonly upregulated or downregulated were identified using publicly available databases GSE66842 and GSE84587. Afterwards, the interactions of DEG products with each other and other proteins were examined using the STRING database. Enrichment analyses of DEGs were performed using the Enrichr-KG web tool including the Gene Ontology Biological Process, KEGG, Jensen_DISEASES and DisGeNET libraries. miRNAs targeting DEGs were detected using miRDB and TargetScanHuman8.0. Results: In HCV-infected cells, the CXCL10 expression is increased in both databases, while the SCGN and H2BC5 (HIST1H2BD) expression is decreased. No direct interaction was found among CXCL10, SCGN, H2BC5 in the top ten proteins. CXCL10 is a member of Hepatitis C and viral protein interactions with cytokine and cytokine receptor KEGG pathways. H2BC5 is a member of viral carcinogenesis KEGG pathways. Predicted overlapping miRNAs targeted by common DEGs were as follows: 59 were where CXCL10 was the estimated target, 22 where SCGN was the estimated target and 29 where H2BC5 (HIST1H2BD) was the estimated target. Conclusions: Our study identified genes that were upregulated or downregulated in HCV-infected cells in both databases and miRNAs associated with these genes, using two different databases. This study creates groundwork for future studies to investigate whether these genes can predict HCV prognosis and HCV-associated HCC development.
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Affiliation(s)
- Çiğdem Yıldırım
- Department of Infectious Diseases and Clinical Microbiology, Nigde Training and Research Hospital, 51100 Nigde, Turkey; (A.İ.); (O.S.)
| | - Fatih Yay
- Clinical Biochemistry Laboratory, Nigde Training and Research Hospital, 51100 Nigde, Turkey;
| | - Ayfer İmre
- Department of Infectious Diseases and Clinical Microbiology, Nigde Training and Research Hospital, 51100 Nigde, Turkey; (A.İ.); (O.S.)
| | - Orçun Soysal
- Department of Infectious Diseases and Clinical Microbiology, Nigde Training and Research Hospital, 51100 Nigde, Turkey; (A.İ.); (O.S.)
| | - Hasan Çağrı Yıldırım
- Department of Medical Oncology, Nigde Training and Research Hospital, 51100 Nigde, Turkey;
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7
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Zhang Y, Guo Y, Yang H, Miao X, Feng Q. DNA tetrahedral scaffold-corbelled self-feedback circuit for dual-mode ratiometric biosensing with Ru@COF-LZU1 accelerator. Biosens Bioelectron 2024; 261:116520. [PMID: 38924812 DOI: 10.1016/j.bios.2024.116520] [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: 04/27/2024] [Revised: 06/06/2024] [Accepted: 06/21/2024] [Indexed: 06/28/2024]
Abstract
Sensitive, reliable, and specific detection of microRNAs (miRNAs) is a key objective for disease diagnosis and prognosis. Here, a ratiometric fluorescent/electrochemiluminescent (FL/ECL) sensor was designed for the dual-mode detection of miRNA-122, a hepatocellular carcinoma biomarker. The strong ECL emission was achieved from imine-linked covalent organic framework (COF-LZU1) accelerator enriched Ru(bpy)32+ molecules (Ru@COF-LZU1), which was applied as a delimited reaction micro-reactor to enhance ECL emission. Impressively, to construct an efficient sensing platform, self-feedback circuit was grafted at the vertex of DNA tetrahedral scaffold (DTS), which could provide a solution-phase-like environment and transform miRNA-122 into abundant single-stranded DNAs on the disposable electrode. Simultaneously, the carboxyfluorescein (FAM) tagged DNA segment was cleaved and released into the reaction solution, bringing in the recovery of FL response (FL on). Finally, the introduction of glucose oxidase (GOD) could generate H2O2 by in situ catalyzing GOD to glucose, resulting in the decrease of ECL signal (ECL off). Relying on FL/ECL ratio value, miRNA-122 was quantified with high sensitivity, well selectivity, stability and favorable practicability, suggesting that the proposed biosensor hold great potential for clinical diagnosis.
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Affiliation(s)
- Yan Zhang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, PR China.
| | - Yuehua Guo
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, PR China
| | - Huan Yang
- School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, PR China
| | - Xiangmin Miao
- School of Life Science, Jiangsu Normal University, Xuzhou, 221116, PR China
| | - Qiumei Feng
- School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, PR China.
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8
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Żychowska J, Ćmil M, Skórka P, Olejnik-Wojciechowska J, Plewa P, Bakinowska E, Kiełbowski K, Pawlik A. The Role of Epigenetic Mechanisms in the Pathogenesis of Hepatitis C Infection. Biomolecules 2024; 14:986. [PMID: 39199374 PMCID: PMC11352264 DOI: 10.3390/biom14080986] [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: 08/07/2024] [Accepted: 08/08/2024] [Indexed: 09/01/2024] Open
Abstract
Hepatitis C virus (HCV) is a hepatotropic virus that can be transmitted through unsafe medical procedures, such as injections, transfusions, and dental treatment. The infection may be self-limiting or manifest as a chronic form that induces liver fibrosis, cirrhosis, or progression into hepatocellular carcinoma (HCC). Epigenetic mechanisms are major regulators of gene expression. These mechanisms involve DNA methylation, histone modifications, and the activity of non-coding RNAs, which can enhance or suppress gene expression. Abnormal activity or the dysregulated expression of epigenetic molecules plays an important role in the pathogenesis of various pathological disorders, including inflammatory diseases and malignancies. In this review, we summarise the current evidence on epigenetic mechanisms involved in HCV infection and progression to HCC.
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Affiliation(s)
- Justyna Żychowska
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.Ż.); (M.Ć.); (P.S.); (E.B.); (K.K.)
| | - Maciej Ćmil
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.Ż.); (M.Ć.); (P.S.); (E.B.); (K.K.)
| | - Patryk Skórka
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.Ż.); (M.Ć.); (P.S.); (E.B.); (K.K.)
| | | | - Paulina Plewa
- Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland;
| | - Estera Bakinowska
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.Ż.); (M.Ć.); (P.S.); (E.B.); (K.K.)
| | - Kajetan Kiełbowski
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.Ż.); (M.Ć.); (P.S.); (E.B.); (K.K.)
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (J.Ż.); (M.Ć.); (P.S.); (E.B.); (K.K.)
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Smart A, Gilmer O, Caliskan N. Translation Inhibition Mediated by Interferon-Stimulated Genes during Viral Infections. Viruses 2024; 16:1097. [PMID: 39066259 PMCID: PMC11281336 DOI: 10.3390/v16071097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 07/04/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
Viruses often pose a significant threat to the host through the exploitation of cellular machineries for their own benefit. In the context of immune responses, myriad host factors are deployed to target viral RNAs and inhibit viral protein translation, ultimately hampering viral replication. Understanding how "non-self" RNAs interact with the host translation machinery and trigger immune responses would help in the development of treatment strategies for viral infections. In this review, we explore how interferon-stimulated gene products interact with viral RNA and the translation machinery in order to induce either global or targeted translation inhibition.
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Affiliation(s)
- Alexandria Smart
- Helmholtz Institute for RNA-Based Infection Research, Helmholtz Centre for Infection Research (HIRI-HZI), Josef-Schneider-Strasse 2, 97080 Würzburg, Germany; (A.S.); (O.G.)
| | - Orian Gilmer
- Helmholtz Institute for RNA-Based Infection Research, Helmholtz Centre for Infection Research (HIRI-HZI), Josef-Schneider-Strasse 2, 97080 Würzburg, Germany; (A.S.); (O.G.)
| | - Neva Caliskan
- Helmholtz Institute for RNA-Based Infection Research, Helmholtz Centre for Infection Research (HIRI-HZI), Josef-Schneider-Strasse 2, 97080 Würzburg, Germany; (A.S.); (O.G.)
- Regensburg Center for Biochemistry (RCB), University of Regensburg, 93053 Regensburg, Germany
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Huang J, Zheng S, Li Q, Zhao H, Zhou X, Yang Y, Zhang W, Cao Y. Host miR-146a-3p Facilitates Replication of Infectious Hematopoietic Necrosis Virus by Targeting WNT3a and CCND1. Vet Sci 2024; 11:204. [PMID: 38787176 PMCID: PMC11126136 DOI: 10.3390/vetsci11050204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 04/28/2024] [Accepted: 04/30/2024] [Indexed: 05/25/2024] Open
Abstract
Infectious hematopoietic necrosis virus (IHNV) is a serious pathogen that causes great economic loss to the salmon and trout industry. Previous studies showed that IHNV alters the expression patterns of splenic microRNAs (miRNAs) in rainbow trout. Among the differentially expressed miRNAs, miRNA146a-3p was upregulated by IHNV. However, it is unclear how IHNV utilizes miRNA146a-3p to escape the immune response or promote viral replication. The present study suggested that one multiplicity of infection (MOI) of IHNV induced the most significant miR-146a-3p expression at 1 day post infection (dpi). The upregulation of miR-146a-3p by IHNV was due to viral N, P, M, and G proteins and relied on the interferon (IFN) signaling pathway. Further investigation revealed that Wingless-type MMTV integration site family 3a (WNT3a) and G1/S-specific cyclin-D1-like (CCND1) are the target genes of miRNA-146a-3p. The regulation of IHNV infection by miRNA-146a-3p is dependent on WNT3a and CCND1. MiRNA-146a-3p was required for the downregulation of WNT3a and CCND1 by IHNV. Moreover, we also found that WNT3a and CCND1 are novel proteins that induce the type-I IFN response in RTG-2 cells, and both of them could inhibit the replication of IHNV. Therefore, IHNV-induced upregulation of miRNA-146a-3p promotes early viral replication by suppressing the type-I IFN response by targeting WNT3a and CCND1. This work not only reveals the molecular mechanism of miRNA-146a-3p during IHNV infection but also provides new antiviral targets for IHNV.
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Affiliation(s)
- Jingwen Huang
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
| | - Shihao Zheng
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
| | - Qiuji Li
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
| | - Hongying Zhao
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
| | - Xinyue Zhou
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
| | - Yutong Yang
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
| | - Wenlong Zhang
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
- Northeastern Science Inspection Station, China Ministry of Agriculture Key Laboratory of Animal Pathogen Biology, Harbin 150069, China
| | - Yongsheng Cao
- College of Veterinary Medicine, Northeast Agricultural University, Changjiang Street NO.600, Harbin 150030, China
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11
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Wu L, Zhang Y, Ren J. Targeting non-coding RNAs and N 6-methyladenosine modification in hepatocellular carcinoma. Biochem Pharmacol 2024; 223:116153. [PMID: 38513741 DOI: 10.1016/j.bcp.2024.116153] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 03/08/2024] [Accepted: 03/18/2024] [Indexed: 03/23/2024]
Abstract
Hepatocellular carcinoma (HCC), the most common form of primary liver cancers, accounts for a significant portion of cancer-related death globally. However, the molecular mechanisms driving the onset and progression of HCC are still not fully understood. Emerging evidence has indicated that non-protein-coding regions of genomes could give rise to transcripts, termed non-coding RNA (ncRNA), forming novel functional driving force for aberrant cellular activity. Over the past decades, overwhelming evidence has denoted involvement of a complex array of molecular function of ncRNAs at different stages of HCC tumorigenesis and progression. In this context, several pre-clinical studies have highlighted the potentials of ncRNAs as novel therapeutic modalities in the management of human HCC. Moreover, N6-methyladenosine (m6A) modification, the most prevalent form of internal mRNA modifications in mammalian cells, is essential for the governance of biological processes within cells. Dysregulation of m6A in ncRNAs has been implicated in human carcinogenesis, including HCC. In this review, we will discuss dysregulation of several hallmark ncRNAs (miRNAs, lncRNAs, and circRNAs) in HCC and address the latest advances for their involvement in the onset and progression of HCC. We also focus on dysregulation of m6A modification and various m6A regulators in the etiology of HCC. In the end, we discussed the contemporary preclinical and clinical application of ncRNA-based and m6A-targeted therapies in HCC.
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Affiliation(s)
- Lin Wu
- Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China
| | - Yingmei Zhang
- Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China
| | - Jun Ren
- Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
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Cordoba-Caballero J, Perkins JR, García-Criado F, Gallego D, Navarro-Sánchez A, Moreno-Estellés M, Garcés C, Bonet F, Romá-Mateo C, Toro R, Perez B, Sanz P, Kohl M, Rojano E, Seoane P, Ranea JAG. Exploring miRNA-target gene pair detection in disease with coRmiT. Brief Bioinform 2024; 25:bbae060. [PMID: 38436559 PMCID: PMC10939301 DOI: 10.1093/bib/bbae060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 12/14/2023] [Accepted: 01/10/2024] [Indexed: 03/05/2024] Open
Abstract
A wide range of approaches can be used to detect micro RNA (miRNA)-target gene pairs (mTPs) from expression data, differing in the ways the gene and miRNA expression profiles are calculated, combined and correlated. However, there is no clear consensus on which is the best approach across all datasets. Here, we have implemented multiple strategies and applied them to three distinct rare disease datasets that comprise smallRNA-Seq and RNA-Seq data obtained from the same samples, obtaining mTPs related to the disease pathology. All datasets were preprocessed using a standardized, freely available computational workflow, DEG_workflow. This workflow includes coRmiT, a method to compare multiple strategies for mTP detection. We used it to investigate the overlap of the detected mTPs with predicted and validated mTPs from 11 different databases. Results show that there is no clear best strategy for mTP detection applicable to all situations. We therefore propose the integration of the results of the different strategies by selecting the one with the highest odds ratio for each miRNA, as the optimal way to integrate the results. We applied this selection-integration method to the datasets and showed it to be robust to changes in the predicted and validated mTP databases. Our findings have important implications for miRNA analysis. coRmiT is implemented as part of the ExpHunterSuite Bioconductor package available from https://bioconductor.org/packages/ExpHunterSuite.
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Affiliation(s)
- Jose Cordoba-Caballero
- Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Bulevar Louis Pasteur, 31, Málaga, 29010, Spain
- Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Puerta del Mar University Hospital, Cádiz, Spain
| | - James R Perkins
- Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Bulevar Louis Pasteur, 31, Málaga, 29010, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), C/ Severo Ochoa, 35, Parque Tecnológico de Andalucía (PTA), Campanillas, Málaga, 29590, Spain
| | - Federico García-Criado
- Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Bulevar Louis Pasteur, 31, Málaga, 29010, Spain
| | - Diana Gallego
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain
- Instituto de Investigación Sanitaria IdiPaZ, Madrid, Spain
| | - Alicia Navarro-Sánchez
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Departament de Fisiologia, Facultat de Medicina i Odontologia, Universitat de València, Av. Blasco Ibáñez 15, 46010, València, Spain
| | - Mireia Moreno-Estellés
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina de Valencia, Jaime Roig 11, 46010, Valencia, Spain
| | - Concepción Garcés
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Departament de Fisiologia, Facultat de Medicina i Odontologia, Universitat de València, Av. Blasco Ibáñez 15, 46010, València, Spain
| | - Fernando Bonet
- Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Puerta del Mar University Hospital, Cádiz, Spain
- Medicine Department, School of Medicine, University of Cádiz, Cádiz, Spain
| | - Carlos Romá-Mateo
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Departament de Fisiologia, Facultat de Medicina i Odontologia, Universitat de València, Av. Blasco Ibáñez 15, 46010, València, Spain
- Incliva Biomedical Research Institute, 46010, València, Spain
| | - Rocio Toro
- Research Unit, Biomedical Research and Innovation Institute of Cádiz (INiBICA), Puerta del Mar University Hospital, Cádiz, Spain
- Medicine Department, School of Medicine, University of Cádiz, Cádiz, Spain
| | - Belén Perez
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain
- Instituto de Investigación Sanitaria IdiPaZ, Madrid, Spain
| | - Pascual Sanz
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Consejo Superior de Investigaciones Científicas, Instituto de Biomedicina de Valencia, Jaime Roig 11, 46010, Valencia, Spain
| | - Matthias Kohl
- Faculty of Medical and Life Sciences, Furtwangen University, Germany
| | - Elena Rojano
- Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Bulevar Louis Pasteur, 31, Málaga, 29010, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), C/ Severo Ochoa, 35, Parque Tecnológico de Andalucía (PTA), Campanillas, Málaga, 29590, Spain
| | - Pedro Seoane
- Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Bulevar Louis Pasteur, 31, Málaga, 29010, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), C/ Severo Ochoa, 35, Parque Tecnológico de Andalucía (PTA), Campanillas, Málaga, 29590, Spain
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
| | - Juan A G Ranea
- Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Bulevar Louis Pasteur, 31, Málaga, 29010, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA-Plataforma BIONAND), C/ Severo Ochoa, 35, Parque Tecnológico de Andalucía (PTA), Campanillas, Málaga, 29590, Spain
- CIBER de Enfermedades Raras (CIBERER), Avda. Monforte de Lemos, 3-5, Pabellón 11, Planta 0, Madrid, 28029, Spain
- Instituto Nacional de Bioinformática (INB/ELIXIR-ES), Instituto de Salud Carlos III (ISCIII), C/ Sinesio Delgado, 4, Madrid, 28029, Spain
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13
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Pandita S, Verma A, Kumar N. Role of miRNAs in regulating virus replication. ANIMAL GENE 2023; 30:200162. [DOI: 10.1016/j.angen.2023.200162] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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14
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Zhang E, Zhang S, Li G, Zhang Z, Liu J. Identification and Verification of Candidate miRNA Biomarkers with Application to Infection with Emiliania huxleyi Virus. Genes (Basel) 2023; 14:1716. [PMID: 37761856 PMCID: PMC10531489 DOI: 10.3390/genes14091716] [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: 07/30/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023] Open
Abstract
The interactions of Emiliania huxleyi and its specific lytic virus (EhV) have a profound influence on marine biogeochemical carbon-sulfur cycles and play a prominent role in global climate change. MicroRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential due to their role in virus-host interactions. However, the application of miRNA signatures as diagnostic markers in marine viral infection has made limited progress. Based on our previous small-RNA sequencing data, one host miRNA biomarker that is upregulated in early infection and seven viral miRNA biomarkers that are upregulated in late infection were identified and verified using qRT-PCR and a receiver operating characteristic curve analysis in pure culture, mixed culture, and natural seawater culture. The host ehx-miR20-5p was able to significantly differentiate infection groups from the control in the middle (24 h post-infection, hpi) and late infection (48 hpi) phases, while seven virus-derived miRNA biomarkers could diagnose the early and late stages of EhV infection. Functional enrichment analysis showed that these miRNAs participated in numerous essential metabolic pathways, including gene transcription and translation, cell division-related pathways, protein-degradation-related processes, and lipid metabolism. Additionally, a dual-luciferase reporter assay confirmed the targeted relationship between a viral ehv-miR7-5p and the host dihydroceramide desaturase gene (hDCD). This finding suggests that the virus-derived miRNA has the ability to inhibit the host sphingolipid metabolism, which is a specific characteristic of EhV infection during the late stage. Our data revealed a cluster of potential miRNA biomarkers with significant regulatory functions that could be used to diagnose EhV infection, which has implications for assessing the infectious activity of EhV in a natural marine environment.
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Affiliation(s)
| | | | | | | | - Jingwen Liu
- College of Ocean Food and Biological Engineering, Jimei University, No. 43, Jiyuan Road, Xiamen 361021, China; (E.Z.); (S.Z.); (G.L.); (Z.Z.)
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15
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Bamunuarachchi G, Vaddadi K, Yang X, Dang Q, Zhu Z, Hewawasam S, Huang C, Liang Y, Guo Y, Liu L. MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1. J Innate Immun 2023; 15:647-664. [PMID: 37607510 PMCID: PMC10601686 DOI: 10.1159/000532063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 07/11/2023] [Indexed: 08/24/2023] Open
Abstract
An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase 1 (TNKS1), and the endogenous small noncoding RNA, miR-9-1, in influenza A virus (IAV) infection. Increased expression of TNKS1 was observed in IAV-infected human lung epithelial cells and mouse lungs. TNKS1 knockdown by RNA interference repressed influenza viral replication. A screen using TNKS1 3'-untranslation region (3'-UTR) reporter assays and predicted microRNAs identified that miR-9-1 targeted TNKS1. Overexpression of miR-9-1 reduced influenza viral replication in lung epithelial cells as measured by viral mRNA and protein levels as well as virus production. miR-9-1 induced type I interferon production and enhanced the phosphorylation of STAT1 in cell culture. The ectopic expression of miR-9-1 in the lungs of mice by using an adenoviral viral vector enhanced type I interferon response, inhibited viral replication, and reduced susceptibility to IAV infection. Our results indicate that miR-9-1 is an anti-influenza microRNA that targets TNKS1 and enhances cellular antiviral state.
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Affiliation(s)
- Gayan Bamunuarachchi
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Kishore Vaddadi
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Xiaoyun Yang
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Quanjin Dang
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Zhengyu Zhu
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Sankha Hewawasam
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Chaoqun Huang
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Yurong Liang
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Yujie Guo
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
| | - Lin Liu
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, OK, USA
- Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, USA
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16
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Vaddadi K, Gandikota C, Huang C, Liang Y, Liu L. Cellular microRNAs target SARS-CoV-2 spike protein and restrict viral replication. Am J Physiol Cell Physiol 2023; 325:C420-C428. [PMID: 37399496 PMCID: PMC10390048 DOI: 10.1152/ajpcell.00516.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 06/12/2023] [Accepted: 06/27/2023] [Indexed: 07/05/2023]
Abstract
MicroRNAs (miRNAs) regulate gene expression posttranscriptionally and are implicated in viral replication and host tropism. miRNAs can impact the viruses either by directly interacting with the viral genome or modulating host factors. Although many miRNAs have predicted binding sites in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA genome, little experimental validation has been done. We first identified 492 miRNAs that have binding site(s) on the spike (S) viral RNA by a bioinformatics prediction. We then validated the selected 39 miRNAs by examining S-protein levels after coexpressing the S-protein and a miRNA into the cells. Seven miRNAs were found to reduce the S-protein levels by more than 50%. Among them, miR-15a, miR-153, miR-298, miR-508, miR-1909, and miR-3130 also significantly reduced SARS-CoV-2 viral replication. SARS-CoV-2 infection decreased the expression levels of miR-298, miR-497, miR-508, miR-1909, and miR-3130, but had no significant effects on miR-15a and miR-153 levels. Intriguingly, the targeting sequences of these miRNAs on the S viral RNA showed sequence conservation among the variants of concern. Our results suggest that these miRNAs elicit effective antiviral defense against SARS-CoV-2 by modulating S-protein expression and are likely targeting all the variants. Thus, the data signify the therapeutic potential of miRNA-based therapy for SARS-CoV-2 infections.NEW & NOTEWORTHY MicroRNAs can impact viruses either by directly interacting with the virus genome or by modulating host factors. We identified that cellular miRNAs regulate effective antiviral defense against SARS-CoV-2 via modulating spike protein expression, which may offer a potential candidate for antiviral therapy.
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Affiliation(s)
- Kishore Vaddadi
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, United States
- The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States
| | - Chaitanya Gandikota
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, United States
- The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States
| | - Chaoqun Huang
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, United States
- The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States
| | - Yurong Liang
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, United States
- The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States
| | - Lin Liu
- Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, United States
- The Lundberg-Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, United States
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17
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Min J, Li Y, Li X, Wang M, Li H, Bi Y, Xu P, Liu W, Ye X, Li J. The circRNA circVAMP3 restricts influenza A virus replication by interfering with NP and NS1 proteins. PLoS Pathog 2023; 19:e1011577. [PMID: 37603540 PMCID: PMC10441791 DOI: 10.1371/journal.ppat.1011577] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 07/24/2023] [Indexed: 08/23/2023] Open
Abstract
Circular RNAs (circRNAs) are involved in various biological roles, including viral infection and antiviral immune responses. To identify influenza A virus (IAV) infection-related circRNAs, we compared the circRNA profiles of A549 cells upon IAV infection. We found that circVAMP3 is substantially upregulated after IAV infection or interferon (IFN) stimulation. Furthermore, IAV and IFN-β induced the expression of QKI-5, which promoted the biogenesis of circVAMP3. Overexpression of circVAMP3 inhibited IAV replication, while circVAMP3 knockdown promoted viral replication, suggesting that circVAMP3 restricts IAV replication. We verified the effect of circVAMP3 on viral infection in mice and found that circVAMP3 restricted IAV replication and pathogenesis in vivo. We also found that circVAMP3 functions as a decoy to the viral proteins nucleoprotein (NP) and nonstructural protein 1 (NS1). Mechanistically, circVAMP3 interfered with viral ribonucleoprotein complex activity by reducing the interaction of NP with polymerase basic 1, polymerase basic 2, or vRNA and restored the activation of IFN-β by alleviating the inhibitory effect of NS1 to RIG-I or TRIM25. Our study provides new insights into the roles of circRNAs, both in directly inhibiting virus replication and in restoring innate immunity against IAV infection.
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Affiliation(s)
- Jie Min
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
| | - Yucen Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China
| | - Xinda Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
| | - Mingge Wang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- School of Life Sciences, University of Science and Technology of China, Anhui, China
| | - Huizi Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
| | - Yuhai Bi
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
| | - Ping Xu
- Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Wenjun Liu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
- Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China
| | - Xin Ye
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
| | - Jing Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
- Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, United States of America
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18
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Hicks SD, Zhu D, Sullivan R, Kannikeswaran N, Meert K, Chen W, Suresh S, Sethuraman U. Saliva microRNA Profile in Children with and without Severe SARS-CoV-2 Infection. Int J Mol Sci 2023; 24:8175. [PMID: 37175883 PMCID: PMC10179619 DOI: 10.3390/ijms24098175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/27/2023] [Accepted: 04/29/2023] [Indexed: 05/15/2023] Open
Abstract
Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) may impair immune modulating host microRNAs, causing severe disease. Our objectives were to determine the salivary miRNA profile in children with SARS-CoV-2 infection at presentation and compare the expression in those with and without severe outcomes. Children <18 years with SARS-CoV-2 infection evaluated at two hospitals between March 2021 and February 2022 were prospectively enrolled. Severe outcomes included respiratory failure, shock or death. Saliva microRNAs were quantified with RNA sequencing. Data on 197 infected children (severe = 45) were analyzed. Of the known human miRNAs, 1606 (60%) were measured and compared across saliva samples. There were 43 miRNAs with ≥2-fold difference between severe and non-severe cases (adjusted p-value < 0.05). The majority (31/43) were downregulated in severe cases. The largest between-group differences involved miR-4495, miR-296-5p, miR-548ao-3p and miR-1273c. These microRNAs displayed enrichment for 32 gene ontology pathways including viral processing and transforming growth factor beta and Fc-gamma receptor signaling. In conclusion, salivary miRNA levels are perturbed in children with severe COVID-19, with the majority of miRNAs being down regulated. Further studies are required to validate and determine the utility of salivary miRNAs as biomarkers of severe COVID-19.
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Affiliation(s)
- Steven D. Hicks
- Department of Pediatrics, Pennsylvania State University Medical Center, Hershey, PA 17033, USA; (S.D.H.)
| | - Dongxiao Zhu
- Department of Computer Science, Wayne State University, Detroit, MI 48201, USA;
| | - Rhea Sullivan
- Department of Pediatrics, Pennsylvania State University Medical Center, Hershey, PA 17033, USA; (S.D.H.)
| | - Nirupama Kannikeswaran
- Division of Emergency Medicine, Department of Pediatrics, Children’s Hospital of Michigan, Central Michigan University, Detroit, MI 48201, USA
| | - Kathleen Meert
- Division of Critical Care, Department of Pediatrics, Children’s Hospital of Michigan, Central Michigan University, Detroit, MI 48201, USA
| | - Wei Chen
- Population Science, Department of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USA
| | - Srinivasan Suresh
- Department of Pediatrics, University of Pittsburgh, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA
| | - Usha Sethuraman
- Division of Emergency Medicine, Department of Pediatrics, Children’s Hospital of Michigan, Central Michigan University, Detroit, MI 48201, USA
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19
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Association of Dengue Virus Serotypes 1&2 with Severe Dengue Having Deletions in Their 3′Untranslated Regions (3′UTRs). Microorganisms 2023; 11:microorganisms11030666. [PMID: 36985238 PMCID: PMC10057630 DOI: 10.3390/microorganisms11030666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/19/2023] [Accepted: 01/30/2023] [Indexed: 03/08/2023] Open
Abstract
Dengue virus infections are recorded as hyper-endemic in many countries, including India. Research pertaining to the reasons for frequent outbreaks and severe dengue is ongoing. Hyderabad city, India, has been recorded as a ‘hotspot’ for dengue virus infections. Dengue virus strains circulating over the past few years in Hyderabad city have been characterized at the molecular level to analyze the serotype/genotypes; 3′UTRs were further amplified and sequenced. The disease severity in patients infected with dengue virus strains with complete and 3′UTR deletion mutants was analyzed. Genotype I of the serotype 1 replaced genotype III, which has been circulating over the past few years in this region. Coincidentally, the number of dengue virus infections significantly increased in this region during the study period. Nucleotide sequence analysis suggested twenty-two and eight nucleotide deletions in the 3′UTR of DENV-1. The eight nucleotide deletions observed in the case of DENV-1 3′UTR were the first reported in this instance. A 50 nucleotide deletion was identified in the case of the serotype DENV-2. Importantly, these deletion mutants were found to cause severe dengue, even though they were found to be replication incompetent. This study emphasized the role of dengue virus 3′UTRs on severe dengue and emerging outbreaks.
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20
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Alshahrani SH, Alameri AA, Kahar F, Alexis Ramírez-Coronel A, Fadhel Obaid R, Alsaikhan F, Zabibah RS, Qasim QA, Altalbawy FMA, Fakri Mustafa Y, Mirzaei R, Karampoor S. Overview of the role and action mechanism of microRNA-128 in viral infections. Microb Pathog 2023; 176:106020. [PMID: 36746316 DOI: 10.1016/j.micpath.2023.106020] [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: 10/14/2022] [Revised: 01/21/2023] [Accepted: 01/31/2023] [Indexed: 02/07/2023]
Abstract
Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 (PVRL4) is post-transcriptionally regulated by miR-128, representing possible miRNA targets that can modulate measles virus infection. Of note, the downregulation of seminal exosomes eca-miR-128 is associated with the long-term persistence of Equine arteritis virus (EAV) in the reproductive tract, and this particular miRNA is a putative regulator of chemokine ligand 16 (C-X-C motif) as determined by target prediction analysis. In this review, the latest information on the role and action mechanism of miR-128 in viral infections will be summarized and discussed in detail.
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Affiliation(s)
- Shadia Hamoud Alshahrani
- Medical Surgical Nursing Department, King Khalid University, Almahala, Khamis Mushate, Saudi Arabia
| | - Ameer A Alameri
- Department of Chemistry, University of Babylon, Babylon, Iraq
| | - Fitriani Kahar
- Medic Technology Laboratory, Poltekkes Kemenkes Semarang, Indonesia
| | - Andrés Alexis Ramírez-Coronel
- National University of Education, Azogues, Ecuador; Catholic University of Cuenca, Azogues Campus, Ecuador; University of Palermo, Buenos Aires, Argentina; CES University, Colombia, Azogues, Ecuador
| | - Rasha Fadhel Obaid
- Department of Biomedical Engineering, Al-Mustaqbal University College, Babylon, Iraq
| | - Fahad Alsaikhan
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Kingdom of Saudi Arabia
| | - Rahman S Zabibah
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | | | - Farag M A Altalbawy
- National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza 12613, Egypt; Department of Chemistry, University College of Duba, Tabuk University, Duba 71911, Saudi Arabia
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
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21
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Gao Y, Yong F, Yan M, Wei Y, Wu X. miR-361 and miR-34a suppress foot-and-mouth disease virus proliferation by activating immune response signaling in PK-15 cells. Vet Microbiol 2023; 280:109725. [PMID: 36996618 DOI: 10.1016/j.vetmic.2023.109725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 03/11/2023] [Accepted: 03/18/2023] [Indexed: 03/22/2023]
Abstract
Foot-and-mouth disease (FMD) severely impacts cloven-hoofed live-stock production, leading to serious economic losses and international restriction on the trade of animals and animal products worldwide. MiRNAs serve key roles in viral immunity and regulation. However, the knowledge about miRNAs regulation in FMDV infection is still limited. In this study, we found that FMDV infection caused rapid cytopathic in PK-15 cell. To investigate the miRNAs' function in FMDV infection, we performed knockdown of endogenous Dgcr8 using its specific siRNA and found that interference of Dgcr8 inhibited cellular miRNA expression and increased FMDV production, including viral capsid proteins expression, viral genome copies and virus titer, suggesting that miRNAs play an important role in FMDV infection. To obtain a full perspective on miRNA expression profiling after FMDV infection, we performed miRNA sequencing and found that FMDV infection caused inhibition of miRNA expression in PK-15 cells. Together with the target prediction result, miR-34a and miR-361 were screened for further study. Function study showed that no matter plasmid or mimics-mediated overexpression of miR-34a and miR-361 both suppressed FMDV replication, while inhibition of endogenous miR-34a and miR-361 expression using specific inhibitors significantly increased FMDV replication. Further study showed that miR-34a and miR-361 stimulated IFN-β promoter activity and activated interferon-stimulated response element (ISRE). In addition, ELISA test found that miR-361 and miR-34a increased secretion level of IFN-β and IFN-γ, which may contribute to repression of FMDV replication. This study preliminary revealed that miR-361 and miR-34a inhibited FMDV proliferation via stimulating immune response.
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22
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Megahed F, Tabll A, Atta S, Ragheb A, Smolic R, Petrovic A, Smolic M. MicroRNAs: Small Molecules with Significant Functions, Particularly in the Context of Viral Hepatitis B and C Infection. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:173. [PMID: 36676797 PMCID: PMC9862007 DOI: 10.3390/medicina59010173] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023]
Abstract
A MicroRNA (miRNA) is defined as a small molecule of non-coding RNA (ncRNA). Its molecular size is about 20 nucleotides (nt), and it acts on gene expression's regulation at the post-transcription level through binding to the 3'untranslated regions (UTR), coding sequences, or 5'UTR of the target messenger RNAs (mRNAs), which leads to the suppression or degradation of the mRNA. In recent years, a huge evolution has identified the origin and function of miRNAs, focusing on their important effects in research and clinical applications. For example, microRNAs are key players in HCV infection and have important host cellular factors required for HCV replication and cell growth. Altered expression of miRNAs affects the pathogenicity associated with HCV infection through regulating different signaling pathways that control HCV/immunity interactions, proliferation, and cell death. On the other hand, circulating miRNAs can be used as novel biomarkers and diagnostic tools for HCV pathogenesis and early therapeutic response. Moreover, microRNAs (miRNA) have been involved in hepatitis B virus (HBV) gene expression and advanced antiviral discovery. They regulate HBV/HCV replication and pathogenesis with different pathways involving facilitation, inhibition, activation of the immune system (innate and adaptive), and epigenetic modifications. In this short review, we will discuss how microRNAs can be used as prognostic, diagnostic, and therapeutic tools, especially for chronic hepatitis viruses (HBV and HCV), as well as how they could be used as new biomarkers during infection and advanced treatment.
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Affiliation(s)
- Fayed Megahed
- Nucleic Acid Research Department, Genetic Engineering and Biotechnological Research Institute (GEBRI), City for Scientific Researches and Technological Applications (SRTA-City), Alexandria 21934, Egypt
| | - Ashraf Tabll
- Microbial Biotechnology Department, National Research Centre, Giza 12622, Egypt
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt
| | - Shimaa Atta
- Department of Immunology, Theodor Bilharz Research Institute, Cairo 12411, Egypt
| | - Ameera Ragheb
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt
| | - Robert Smolic
- Faculty of Dental Medicine and Health Osijek, University of Osijek, Crkvena 21, 31000 Osijek, Croatia
| | - Ana Petrovic
- Faculty of Dental Medicine and Health Osijek, University of Osijek, Crkvena 21, 31000 Osijek, Croatia
| | - Martina Smolic
- Faculty of Dental Medicine and Health Osijek, University of Osijek, Crkvena 21, 31000 Osijek, Croatia
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23
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Teimoori A, Mirshahabi H, Khansarinejad B, Soleimanjahi H, Karimi H, Rasti M, Shatizadeh Malekshahi S. Significant alteration of IFN stimulated genes expression in MA104 cells infected with bovine rotavirus RF strain. J Immunoassay Immunochem 2023; 44:56-65. [PMID: 36052996 DOI: 10.1080/15321819.2022.2118061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The pattern recognition receptors (PRRs) trigger signaling cascades, such as nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). Rotavirus (RV) countermeasures against innate responses and understanding of these processes will improve our knowledge regarding immunopathogenesis of RV infection. In this study, we investigated the effect of RV RF strain on the important ISG candidate genes engaging in virus infections for which little information is known in RV RF strain. To this end, MA104 cells were mock/infected with RF followed by incubation in the presence or absence of IFN-α and the expression of MX1, OAS1, STAT1, ISG15, and ISG56 mRNA was analyzed by real-time PCR. All of ISGs' mRNAs showed higher expression levels in IFN I treated cells compared to virus-infected cells except for ISG56. Infecting the cells with RV and treatment with IFN type I led to overexpression of ISG56 compared to cells were either infected with the virus or only treated with IFN I. In conclusion, we showed that the RV RF strain efficiently blocks type I IFN-induced gene expression particularly ISG15, MX1, STAT, and OSA1 as antiviral proteins. Furthermore, viruses may use some ISGs such as ISG 56 to regulate IFN I signaling pathway, negatively.
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Affiliation(s)
- Ali Teimoori
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.,Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Hessam Mirshahabi
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.,Department of Microbiology and Virology, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Behzad Khansarinejad
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.,Department of Microbiology and Immunology, Arak University of Medical Sciences, Arak, Iran
| | - Hoorieh Soleimanjahi
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hesam Karimi
- Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mojtaba Rasti
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Abstract
Dendritic cells (DCs) are key regulators of both innate and adaptive immunity via varied functions, including cytokine production and antigen presentation. Plasmacytoid DC (pDC) is a DC subset specialized in the production of type I and III interferons (IFNs). They are thus pivotal players of the host antiviral response during the acute phase of infection by genetically distant viruses. The pDC response is primarily triggered by the endolysosomal sensors Toll-like receptors, which recognize nucleic acids from pathogens. In some pathologic contexts, pDC response can also be triggered by host nucleic acids, hereby contributing to the pathogenesis of autoimmune diseases, such as, e.g., systemic lupus erythematosus. Importantly, recent in vitro studies from our laboratory and others uncovered that pDCs sense viral infections when a physical contact is established with infected cells. This specialized synapse-like feature enables a robust type I and III IFN secretion at the infected site. Therefore, this concentrated and confined response likely limits the correlated deleterious impacts of excessive cytokine production to the host, notably due to tissue damages. Here we provide a pipeline of methods for ex vivo studies of pDC antiviral functions, designed to address how pDC activation is regulated by cell-cell contact with virally infected cells and the current approaches enabling to decipher the underlying molecular events leading to an efficient antiviral response.
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25
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Abdel Halim AS, Rudayni HA, Chaudhary AA, Ali MAM. MicroRNAs: Small molecules with big impacts in liver injury. J Cell Physiol 2023; 238:32-69. [PMID: 36317692 DOI: 10.1002/jcp.30908] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/30/2022] [Accepted: 10/14/2022] [Indexed: 11/07/2022]
Abstract
A type of small noncoding RNAs known as microRNAs (miRNAs) fine-tune gene expression posttranscriptionally by binding to certain messenger RNA targets. Numerous physiological processes in the liver, such as differentiation, proliferation, and apoptosis, are regulated by miRNAs. Additionally, there is growing evidence that miRNAs contribute to liver pathology. Extracellular vesicles like exosomes, which contain secreted miRNAs, may facilitate paracrine and endocrine communication between various tissues by changing the gene expression and function of distal cells. The use of stable miRNAs as noninvasive biomarkers was made possible by the discovery of these molecules in body fluids. Circulating miRNAs reflect the conditions of the liver that are abnormal and may serve as new biomarkers for the early detection, prognosis, and evaluation of liver pathological states. miRNAs are appealing therapeutic targets for a range of liver disease states because altered miRNA expression is associated with deregulation of the liver's metabolism, liver damage, liver fibrosis, and tumor formation. This review provides a comprehensive review and update on miRNAs biogenesis pathways and mechanisms of miRNA-mediated gene silencing. It also outlines how miRNAs affect hepatic cell proliferation, death, and regeneration as well as hepatic detoxification. Additionally, it highlights the diverse functions that miRNAs play in the onset and progression of various liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, fibrosis, hepatitis C virus infection, and hepatocellular carcinoma. Further, it summarizes the diverse liver-specific miRNAs, illustrating the potential merits and possible caveats of their utilization as noninvasive biomarkers and appealing therapeutic targets for liver illnesses.
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Affiliation(s)
- Alyaa S Abdel Halim
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Hassan Ahmed Rudayni
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Anis Ahmad Chaudhary
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Mohamed A M Ali
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.,Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
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26
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Hassuna NA, Gamil AN, Mahmoud MS, Mohamed WK, Khairy R. Circulating microRNAs as predictors of response to sofosbuvir + daclatasvir + ribavirin in in HCV genotype-4 Egyptian patients. BMC Gastroenterol 2022; 22:499. [PMID: 36463118 PMCID: PMC9719120 DOI: 10.1186/s12876-022-02485-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 08/09/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) play an important role in various diseases, including HCV infection, the aim of the current study was to evaluate the potential use of serum miRNAs as biomarkers for diagnosis, prognosis, and prediction of responses to direct acting antivirals (sofosbuvir + daclatasvir + ribavirin) in HCV-4 patients. METHODS The serum expression profiles of four liver-associated miRNAs (miRNA-122, 155, 196 and 29) were assessed in 160 HCV-4 patients and 50 healthy controls using real-time PCR prior to therapy. RESULTS miR-122 and miR-155 showed upregulation in HCV-4 patients compared to healthy controls while miR-196 and miR-29 showed downregulation in HCV-4 patients. ROC curve analyses revealed that the four-studied miRNAs could be valuable biomarkers for predicting response to DAAs with AUC 0.973 for miR-122, 0.878 for miR-155, 0.808 for miR-29 and 0.874 for miR-196 respectively. Univariate logistic regression analysis revealed that miR-196 level is positive predictor for SVR, whereas miR-122,155 levels are negative predictors of response. Multivariate logistic regression analysis revealed that miR-196 is the most significant in predicting response to treatment (p value = 0.011). CONCLUSION To the best of our knowledge, the current study provided the first clinical evidence of the potential use of circulating miRNAs (miR; 122, 155, 196 and 29) as biomarkers of CHC in HCV-4 patients receiving the new DAA regimen (SOF/DAV + RIB), which is a strong motivator for further studies.
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Affiliation(s)
- Noha Anwar Hassuna
- grid.411806.a0000 0000 8999 4945Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Aya Nabil Gamil
- grid.411806.a0000 0000 8999 4945Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Mahmoud Shokry Mahmoud
- grid.411806.a0000 0000 8999 4945Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Wafaa Khairy Mohamed
- grid.411806.a0000 0000 8999 4945Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
| | - Rasha Khairy
- grid.411806.a0000 0000 8999 4945Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt
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27
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Periwal N, Bhardwaj U, Sarma S, Arora P, Sood V. In silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs. Front Cell Infect Microbiol 2022; 12:966870. [PMID: 36519126 PMCID: PMC9742375 DOI: 10.3389/fcimb.2022.966870] [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: 06/11/2022] [Accepted: 10/05/2022] [Indexed: 11/29/2022] Open
Abstract
The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 has resulted in enormous deaths around the world. Clues from genomic sequences of parent and their mutants can be obtained to understand the evolving pathogenesis of this virus. Apart from the viral proteins, virus-encoded microRNAs (miRNAs) have been shown to play a vital role in regulating viral pathogenesis. Thus we sought to investigate the miRNAs encoded by SARS-CoV-2, its mutants, and the host. Here, we present the results obtained using a dual approach i.e (i) identifying host-encoded miRNAs that might regulate viral pathogenesis and (ii) identifying viral-encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing the first approach resulted in the identification of ten host-encoded miRNAs that could target the SARS, SARS-CoV-2, and its mutants. Interestingly our analysis revealed that there is a significantly higher number of host miRNAs that could target the SARS-CoV-2 genome as compared to the SARS reference genome. Results from the second approach resulted in the identification of a set of virus-encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar "GA" rich motif in the SARS-CoV-2 and its mutant genomes that was shown to play a vital role in lung pathogenesis during severe SARS infections. In summary, we have identified human and virus-encoded miRNAs that might regulate the pathogenesis of SARS coronaviruses and describe similar non-coding RNA sequences in SARS-CoV-2 that were shown to regulate SARS-induced lung pathology in mice.
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Affiliation(s)
- Neha Periwal
- Department of Biochemistry, Jamia Hamdard, New Delhi, India
| | | | - Sankritya Sarma
- Department of Zoology, Hansraj College, University of Delhi, Delhi, India
| | - Pooja Arora
- Department of Zoology, Hansraj College, University of Delhi, Delhi, India
| | - Vikas Sood
- Department of Biochemistry, Jamia Hamdard, New Delhi, India,*Correspondence: Vikas Sood,
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28
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Min J, Liu W, Li J. Emerging Role of Interferon-Induced Noncoding RNA in Innate Antiviral Immunity. Viruses 2022; 14:2607. [PMID: 36560611 PMCID: PMC9780829 DOI: 10.3390/v14122607] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/21/2022] [Accepted: 11/21/2022] [Indexed: 11/24/2022] Open
Abstract
Thousands of unique noncoding RNAs (ncRNAs) exist within the genomes of higher eukaryotes. Upon virus infection, the host generates interferons (IFNs), which initiate the expression of hundreds of interferon-stimulated genes (ISGs) through IFN receptors on the cell surface, establishing a barrier as the host's antiviral innate immunity. With the development of novel RNA-sequencing technology, many IFN-induced ncRNAs have been identified, and increasing attention has been given to their functions as regulators involved in the antiviral innate immune response. IFN-induced ncRNAs regulate the expression of viral proteins, IFNs, and ISGs, as well as host genes that are critical for viral replication, cytokine and chemokine production, and signaling pathway activation. This review summarizes the complex regulatory role of IFN-induced ncRNAs in antiviral innate immunity from the above aspects, aiming to improve understanding of ncRNAs and provide reference for the basic research of antiviral innate immunity.
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Affiliation(s)
- Jie Min
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wenjun Liu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China
- Institute of Microbiology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Beijing 100101, China
| | - Jing Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China
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29
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Hassan M, El-Ahwany E, Elzallat M, Rahim AA, Abu-Taleb H, Abdelrahman Y, Hassanein M. Role of MicroRNAs in the Development of Chronic Liver Disease in Hepatitis Virus-Infected Egyptian Population. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.10902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background: The identification of miRNAs that play a role in the regulation of the viral life cycle and its related liver illness opens the door to the development of diagnostic biomarkers that can categorize patients at higher risk for developing end-stage liver disease. This study was designed to investigate the role of miRNAs in the development of viral hepatitis-induced chronic liver disease (CLD) in the Egyptian population, as well as their potential as possible diagnostic biomarkers for chronic hepatitis virus infection.
Methodology: The study involved 100 CLD patients; 55 cases of hepatitis C virus (HCV) and 45 cases of non-viral hepatitis, in addition to 40 healthy controls. The expression of five miRNAs (miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431) was assessed using real-time PCR.
Results: Serum levels of miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431 were significantly higher in all patients than the control group (p<0.01). Also, they were significantly greater in viral hepatitis cases compared to the non-viral hepatitis group (p<0.01). The sensitivities and specificities of miR-122a, miR‐30, miR‐296, miR‐351, and miR‐431 were (85.71%, 83.33%), (82.35%, 83.33%), (85.71%, 69.44%), (88.64%, 75.76%), and (87.80%, 65.79%), respectively.
Conclusions: miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431 play key roles in the development of CLD as a consequence of viral infection. So, they have the potential to be targeted for the early detection of chronic hepatitis virus infection and allow for exploring a new frontier in the discovery of innovative therapeutics to combat chronic viral infection and its serious life-threatening complications including liver cancer.
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30
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Shan J, Zhou P, Liu Z, Zheng K, Jin X, Du L. Association of miRNA-146a Gene Polymorphism Rs2910164 with Behcet's Disease: A Meta-analysis. Ocul Immunol Inflamm 2022; 30:1883-1889. [PMID: 34403295 DOI: 10.1080/09273948.2021.1968002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND A meta-analysis was performed by summarizing relevant researches to evaluate the relationship between miRNA-146a gene polymorphism rs2910164 and Behcet's disease (BD). METHODS A systematic search of published studies was conducted in PubMed and Embase. Five eligible studies involving 1167 BD cases and 1662 controls were included in the current meta-analysis. RESULTS The results suggested that the polymorphism rs2910164 was correlated with BD susceptibility in all genetic models. In subgroup analysis according to ethnicity, the relationship between this polymorphism and BD was more significant in Caucasians (allele model: OR = 0.49, 95% CI 0.39-0.61; heterozygote model: OR = 0.35, 95% CI 0.26-0.47; homozygote model: OR = 0.29, 95% CI 0.16-0.53; dominant model: OR = 0.34, 95% CI 0.25-0.45; recessive model: OR = 0.56, 95% CI 0.50-0.72) than that in Asians. CONCLUSION In conclusion, this meta-analysis indicates that miRNA-146a gene polymorphism rs2910164 G allele confers BD susceptibility, especially in Caucasians.
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Affiliation(s)
- Jiankang Shan
- The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, P.R. China
| | - Pengyi Zhou
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, P.R. China
| | - Zhenzhen Liu
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, P.R. China
| | - Kaifeng Zheng
- The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, P.R. China
| | - Xuemin Jin
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, P.R. China
| | - Liping Du
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, P.R. China
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Micro-Players of Great Significance-Host microRNA Signature in Viral Infections in Humans and Animals. Int J Mol Sci 2022; 23:ijms231810536. [PMID: 36142450 PMCID: PMC9504570 DOI: 10.3390/ijms231810536] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/04/2022] [Accepted: 09/08/2022] [Indexed: 11/22/2022] Open
Abstract
Over time, more and more is becoming known about micro-players of great significance. This is particularly the case for microRNAs (miRNAs; miR), which have been found to participate in the regulation of many physiological and pathological processes in both humans and animals. One such process is viral infection in humans and animals, in which the host miRNAs—alone or in conjunction with the virus—interact on two levels: viruses may regulate the host’s miRNAs to evade its immune system, while the host miRNAs can play anti- or pro-viral roles. The purpose of this comprehensive review is to present the key miRNAs involved in viral infections in humans and animals. We summarize the data in the available literature, indicating that the signature miRNAs in human viral infections mainly include 12 miRNAs (i.e., miR-155, miR-223, miR-146a, miR-122, miR-125b, miR-132, miR-34a, miR -21, miR-16, miR-181 family, let-7 family, and miR-10a), while 10 miRNAs are commonly found in animals (i.e., miR-155, miR-223, miR-146a, miR-145, miR-21, miR-15a/miR-16 cluster, miR-181 family, let-7 family, and miR-122) in this context. Knowledge of which miRNAs are involved in different viral infections and the biological functions that they play can help in understanding the pathogenesis of viral diseases, facilitating the future development of therapeutic agents for both humans and animals.
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Abstract
Flaviviruses are a spectrum of vector-borne RNA viruses that cause potentially severe diseases in humans including encephalitis, acute-flaccid paralysis, cognitive disorders and foetal abnormalities. Japanese encephalitis virus (JEV), Zika virus (ZIKV), West Nile virus (WNV) and Dengue virus (DENV) are globally emerging pathogens that lead to epidemics and outbreaks with continued transmission to newer geographical areas over time. In the past decade, studies have focussed on understanding the pathogenic mechanisms of these viruses in a bid to alleviate their disease burden. MicroRNAs (miRNAs) are short single-stranded RNAs that have emerged as master-regulators of cellular gene expression. The dynamics of miRNAs within a cell have the capacity to modulate hundreds of genes and, consequently, their physiological manifestation. Increasing evidence suggests their role in host response to disease and infection including cell survival, intracellular viral replication and immune activation. In this review, we aim to comprehensively update published evidence on the role of miRNAs in host cells infected with the common neurotropic flaviviruses, with an increased focus on neuropathogenic mechanisms. In addition, we briefly cover therapeutic advancements made in the context of miRNA-based antiviral strategies.
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SP1/miR-92a-1-5p/SOCS5: A novel regulatory axis in feline panleukopenia virus replication. Vet Microbiol 2022; 273:109549. [PMID: 36037621 DOI: 10.1016/j.vetmic.2022.109549] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/17/2022] [Accepted: 08/20/2022] [Indexed: 11/20/2022]
Abstract
MicroRNAs (miRNAs) are vital post-transcriptional regulators that participate in host-pathogen interactions by modulating the expression of cellular factors. Previous studies have demonstrated that feline panleukopenia virus (FPV) alters miRNA expression levels within host cells. However, the relationship between FPV replication and host miRNAs remains unclear. Here, we demonstrated that FPV infection significantly altered cellular miR-92a-1-5p expression in F81 cells by upregulating the expression of specificity protein 1 (SP1). Furthermore, we observed that miR-92a-1-5p enhanced interferon (IFN-α/β) expression by targeting the suppressors of cytokine signaling 5 (SOCS5) that negatively regulates NF-κB signaling and inhibits FPV replication in host cells. These findings revealed that miR-92a-1-5p plays a crucial role in host defense against FPV infection.
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Roles of microRNAs in Hepatitis C Virus Replication and Pathogenesis. Viruses 2022; 14:v14081776. [PMID: 36016398 PMCID: PMC9413378 DOI: 10.3390/v14081776] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/11/2022] [Accepted: 08/13/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection is associated with the development of chronic liver diseases, e.g., fibrosis, cirrhosis, even hepatocellular carcinoma, and/or extra-hepatic diseases such as diabetes. As an obligatory intracellular pathogen, HCV absolutely relies on host cells to propagate and is able to modulate host cellular factors in favor of its replication. Indeed, lots of cellular factors, including microRNAs (miRNAs), have been identified to be dysregulated during HCV infection. MiRNAs are small noncoding RNAs that regulate protein synthesis of their targeting mRNAs at the post-transcriptional level, usually by suppressing their target gene expression. The miRNAs dysregulated during HCV infection could directly or indirectly modulate HCV replication and/or induce liver diseases. Regulatory mechanisms of various miRNAs in HCV replication and pathogenesis have been characterized. Some dysregulated miRNAs have been considered as the biomarkers for the detection of HCV infection and/or HCV-related diseases. In this review, we intend to briefly summarize the identified miRNAs functioning at HCV replication and pathogenesis, focusing on the recent developments.
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Vuillier F, Li Z, Black I, Cruciani M, Rubino E, Michel F, Pellegrini S. IFN-I inducible miR-3614-5p targets ADAR1 isoforms and fine tunes innate immune activation. Front Immunol 2022; 13:939907. [PMID: 35935998 PMCID: PMC9354889 DOI: 10.3389/fimmu.2022.939907] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/27/2022] [Indexed: 11/13/2022] Open
Abstract
Regulation of innate immune responses is essential for maintenance of immune homeostasis and development of an appropriate immunity against microbial infection. We show here that miR-3614-5p, product of the TRIM25 host gene, is induced by type I interferon (IFN-I) in several human non-immune and immune cell types, in particular in primary myeloid cells. Studies in HeLa cells showed that miR-3614-5p represses both p110 and p150 ADAR1 and reduces constitutive and IFN-induced A-to-I RNA editing. In line with this, activation of innate sensors and expression of IFN-β and the pro-inflammatory IL-6 are promoted. MiR-3614-5p directly targets ADAR1 transcripts by binding to one specific site in the 3’UTR. Moreover, we could show that endogenous miR-3614-5p is associated with Ago2 and targets ADAR1 in IFN-stimulated cells. Overall, we propose that, by reducing ADAR1, IFN-I-induced miR-3614-5p contributes to lowering the activation threshold of innate sensors. Our findings provide new insights into the role of miR-3614-5p, placing it as a potential fine tuner of dsRNA metabolism, cell homeostasis and innate immunity.
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Affiliation(s)
- Françoise Vuillier
- Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France
| | - Zhi Li
- Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France
| | - Iain Black
- Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France
| | - Melania Cruciani
- Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France
| | - Erminia Rubino
- Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France
| | - Frédérique Michel
- Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France
| | - Sandra Pellegrini
- Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France
- Microenvironment and Immunity Unit, Institut Pasteur, Paris, France
- *Correspondence: Sandra Pellegrini,
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Chang M, Li B, Liao M, Rong X, Wang Y, Wang J, Yu Y, Zhang Z, Wang C. Differential expression of miRNAs in the body wall of the sea cucumber Apostichopus japonicus under heat stress. Front Physiol 2022; 13:929094. [PMID: 35936896 PMCID: PMC9351827 DOI: 10.3389/fphys.2022.929094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 06/27/2022] [Indexed: 11/24/2022] Open
Abstract
MicroRNAs, as one of the post-transcriptional regulation of genes, play an important role in the development process, cell differentiation and immune defense. The sea cucumber Apostichopus japonicus is an important cold-water species, known for its excellent nutritional and economic value, which usually encounters heat stress that affects its growth and leads to significant economic losses. However, there are few studies about the effect of miRNAs on heat stress in sea cucumbers. In this study, high-throughput sequencing was used to analyze miRNA expression in the body wall of sea cucumber between the control group (CS) and the heat stress group (HS). A total of 403 known miRNAs and 75 novel miRNAs were identified, of which 13 miRNAs were identified as significantly differentially expressed miRNAs (DEMs) in response to heat stress. A total of 16,563 target genes of DEMs were predicted, and 101 inversely correlated target genes that were potentially regulated by miRNAs in response to heat stress of sea cucumbers were obtained. Based on these results, miRNA-mRNA regulatory networks were constructed. The expression results of high-throughput sequencing were validated in nine DEMs and four differentially expressed genes (DEGs) by quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, pathway enrichment of target genes suggested that several important regulatory pathways may play an important role in the heat stress process of sea cucumber, including ubiquitin-mediated proteolysis, notch single pathway and endocytosis. These results will provide basic data for future studies in miRNA regulation and molecular adaptive mechanisms of sea cucumbers under heat stress.
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Affiliation(s)
- Mengyang Chang
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- College of Fishers and Life Science, Shanghai Ocean University, Shanghai, China
| | - Bin Li
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Meijie Liao
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
- *Correspondence: Meijie Liao, ; Xiaojun Rong,
| | - Xiaojun Rong
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
- *Correspondence: Meijie Liao, ; Xiaojun Rong,
| | - Yingeng Wang
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Jinjin Wang
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Yongxiang Yu
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Zheng Zhang
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Chunyuan Wang
- Key Laboratory of Sustainable and Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China
- Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
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Vadivalagan C, Shitut A, Kamalakannan S, Chen RM, Serrano-Aroca Á, Mishra V, Aljabali AAA, Singh SK, Chellappan DK, Gupta G, Dua K, El-Tanani M, Tambuwala MM, Krishnan A. Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2. Cell Signal 2022; 95:110334. [PMID: 35461900 PMCID: PMC9022400 DOI: 10.1016/j.cellsig.2022.110334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/13/2022] [Accepted: 04/14/2022] [Indexed: 12/27/2022]
Abstract
Exosome trans-membrane signals provide cellular communication between the cells through transport and/or receiving the signal by molecule, change the functional metabolism, and stimulate and/or inhibit receptor signal complexes. COVID19 genetic transformations are varied in different geographic positions, and single nucleotide polymorphic lineages were reported in the second waves due to the fast mutational rate and adaptation. Several vaccines were developed and in treatment practice, but effective control has yet to reach in cent presence. It was initially a narrow immune-modulating protein target. Controlling these diverse viral strains may inhibit their transuding mechanisms primarily to target RNA genes responsible for COVID19 transcription. Exosomal miRNAs are the main sources of transmembrane signals, and trans-located miRNAs can directly target COVID19 mRNA transcription. This review discussed targeted viral transcription by delivering the artificial miRNA (amiRNA) mediated exosomes in the infected cells and significant resources of exosome and their efficacy.
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Affiliation(s)
- Chithravel Vadivalagan
- Graduate Institute of Medical Sciences, College of medicine, Taipei Medical University, Taipei 110, Taiwan; Department of Biochemistry, AKFA Medical School, AKFA University, Tashkent, Uzbekistan.
| | - Anushka Shitut
- Department of Life Sciences, Christ University, Bhavani, Nagar, Bangalor, Karnataka 560029, India.
| | - Siva Kamalakannan
- National Center for Disease Control, Ministry of Health and Family Welfare, Government of India, New Delhi 110054, India
| | - Ruei-Ming Chen
- Graduate Institute of Medical Sciences, College of medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Ángel Serrano-Aroca
- Biomaterials and Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara, Punjab, India
| | - Alaa A A Aljabali
- Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University-Faculty of Pharmacy, Irbid 21163, Jordan
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T Road, Phagwara, Punjab, India; Faculty of Health, Australian Research Centre in Complementary & Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia
| | - Dinesh Kumar Chellappan
- School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, India
| | - Kamal Dua
- School of Pharmacy, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| | - Mohamed El-Tanani
- Pharmacological and Diagnostic Research Centre, Al-Ahliyya Amman University, Faculty of Pharmacy, Amman, Jordan
| | - Murtaza M Tambuwala
- School of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine, United Kingdom.
| | - Anand Krishnan
- Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa; Department of Chemical Pathology, School of Pathology, National Health Laboratory Services, Bloemfontein, South Africa.
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38
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Kooshkaki O, Asghari A, Mahdavi R, Azarkar G, Parsamanesh N. Potential of MicroRNAs As Biomarkers and Therapeutic Targets in Respiratory Viruses: A Literature Review. DNA Cell Biol 2022; 41:544-563. [PMID: 35699380 DOI: 10.1089/dna.2021.1101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through recognition of cognate sequences and interference of transcriptional, translational, or epigenetic processes. Hundreds of miRNA genes have been found in diverse viruses, and many of these are phylogenetically conserved. Respiratory viruses are the most frequent causative agents of disease in humans, with a significant impact on morbidity and mortality worldwide. Recently, the role of miRNAs in respiratory viral gene regulation, as well as host gene regulation during disease progression, has become a field of interest. This review highlighted the importance of various miRNAs and their potential role in fighting with respiratory viruses as therapeutic molecules with a focus on COVID-19.
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Affiliation(s)
- Omid Kooshkaki
- Department of Hematology, Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Arghavan Asghari
- Department of Hematology, Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.,Department of Hematology, Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Reza Mahdavi
- Department of Hematology, Kerman University of Medical Sciences, Kerman, Iran
| | - Ghodsiyeh Azarkar
- Department of Hematology, Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Negin Parsamanesh
- Department of Hematology, Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Science, Zanjan, Iran
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Wang Q, Wang J, Xu Y, Li Z, Wang B, Li Y. The Interaction of Influenza A NS1 and Cellular TRBP Protein Modulates the Function of RNA Interference Machinery. Front Microbiol 2022; 13:859420. [PMID: 35558132 PMCID: PMC9087287 DOI: 10.3389/fmicb.2022.859420] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 03/29/2022] [Indexed: 11/24/2022] Open
Abstract
Influenza A virus (IAV), one of the most prevalent respiratory diseases, causes pandemics around the world. The multifunctional non-structural protein 1 (NS1) of IAV is a viral antagonist that suppresses host antiviral response. However, the mechanism by which NS1 modulates the RNA interference (RNAi) pathway remains unclear. Here, we identified interactions between NS1 proteins of Influenza A/PR8/34 (H1N1; IAV-PR8) and Influenza A/WSN/1/33 (H1N1; IAV-WSN) and Dicer’s cofactor TAR-RNA binding protein (TRBP). We found that the N-terminal RNA binding domain (RBD) of NS1 and the first two domains of TRBP protein mediated this interaction. Furthermore, two amino acid residues (Arg at position 38 and Lys at position 41) in NS1 were essential for the interaction. We generated TRBP knockout cells and found that NS1 instead of NS1 mutants (two-point mutations within NS1, R38A/K41A) inhibited the process of microRNA (miRNA) maturation by binding with TRBP. PR8-infected cells showed masking of short hairpin RNA (shRNA)-mediated RNAi, which was not observed after mutant virus-containing NS1 mutation (R38A/K41A, termed PR8/3841) infection. Moreover, abundant viral small interfering RNAs (vsiRNAs) were detected in vitro and in vivo upon PR8/3841 infection. We identify, for the first time, the interaction between NS1 and TRBP that affects host RNAi machinery.
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Affiliation(s)
- Qi Wang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.,CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Jiaxin Wang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.,CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Yan Xu
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.,CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Zhe Li
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Binbin Wang
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.,CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
| | - Yang Li
- CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
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40
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Azhar A, Khan WH, Al-Hosaini K, Kamal MA. miRNAs in SARS-CoV-2 Infection: An Update. Curr Drug Metab 2022; 23:283-298. [PMID: 35319361 DOI: 10.2174/1389200223666220321102824] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 01/10/2022] [Accepted: 01/18/2022] [Indexed: 02/08/2023]
Abstract
Coronavirus disease-2019 (COVID-19) is a highly infectious disease caused by newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the inception of SARS-CoV-2 from Wuhan, China, the virus has traveled to more than 200 countries globally. The role of SARS-CoV-2 in COVID-19 has been thoroughly investigated and reviewed in the last 22 months or so; however, a comprehensive outline of miRNAs in SARS-CoV-2 infection is still missing. The genetic material of SARS-CoV-2 is a single-stranded RNA molecule nearly 29 kb in size. RNA is composed of numerous sub-constituents, including microRNAs (miRNAs). miRNAs play an essential role in biological processes like apoptosis, cellular metabolism, cell death, cell movement, oncogenesis, intracellular signaling, immunity, and infection. Lately, miRNAs have been involved in SARS-CoV-2 infection, though the clear demonstration of miRNAs in the SARS-CoV-2 infection is not fully elucidated. The present review article summarizes recent findings of miRNAs associated with SARS-CoV-2 infection. We presented various facets of miRNAs such as miRNAs as the protagonist in viral infection, the occurrence of miRNA in cellular receptors, expression of miRNAs in multiple diseases, miRNA as a biomarker, and miRNA as a therapeutic tool discussed in detail. We also presented the vaccine status available in various countries.
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Affiliation(s)
- Asim Azhar
- Aligarh College of Education, Aligarh, UP, India
| | - Wajihul Hasan Khan
- Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, India
| | - Khaled Al-Hosaini
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Post Box 2457, Riyadh 11451, Kingdom of Saudi Arabia
| | - Mohammad Amjad Kamal
- West China School of Nursing / Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
- King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia
- Enzymoics, NSW; Novel Global Community Educational Foundation, Australia
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41
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Gharib AF, Eed EM, Khalifa AS, Raafat N, Shehab-Eldeen S, Alwakeel HR, Darwiesh E, Essa A. Value of Serum miRNA-96-5p and miRNA-99a-5p as Diagnostic Biomarkers for Hepatocellular Carcinoma. Int J Gen Med 2022; 15:2427-2436. [PMID: 35264879 PMCID: PMC8901257 DOI: 10.2147/ijgm.s354842] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/15/2022] [Indexed: 12/23/2022] Open
Abstract
Purpose Circulatory microRNAs (miRNAs) have the potential to be employed as markers for cancer detection and as prognostic tools for disease management. As a result, our goal was to explore the effectiveness of serum miRNA-96-5p and miRNA-99a-5p as diagnostic tools in hepatocellular carcinoma (HCC). Patients and methods Blood samples were collected from 55 patients with HCV-induced HCC, 55 patients with HCV-induced liver cirrhosis, and 55 healthy controls. The expression levels of miRNA-96-5p and miRNA-99a-5p were measured using quantitative RT-PCR. Results miRNA-96-5p expression levels were increased in HCC patient sera, while miRNA-99a-5p levels were reduced. According to ROC curve analysis, using a combination of circulating miRNA-96-5p, miRNA-99a-5-, and alpha-fetoprotein (AFP) improves the accuracy of diagnoses for HCC, with an area under the curve (AUC) of 0.97, compared to AUCs of 0.82, 0.86, and 0.73, respectively, for the individual biomarkers. Furthermore, the present data suggested that higher serum miRNA-96-5p levels were linked to larger tumors and metastasis, whereas lower serum miRNA-99a-5p levels were exclusively linked to HCC metastasis. Conclusion Using miRNA-96-5p and miRNA-99a-5p in combination with AFP increased both sensitivity and specificity for the diagnosis of HCC. Furthermore, serum levels were linked to tumor size and metastasis. These findings suggested that serum miRNA-96-5p and miRNA-99a-5p could be used as non-invasive biomarkers for the diagnosis of HCC.
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Affiliation(s)
- Amal F Gharib
- Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif, 21944, Saudi Arabia
| | - Emad M Eed
- Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif, 21944, Saudi Arabia
| | - Amany S Khalifa
- Clinical Pathology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
| | - Nermin Raafat
- Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Somaia Shehab-Eldeen
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
- Department of Internal Medicine, College of Medicine, King Faisal University, Al-Ahsaa, Saudi Arabia
- Correspondence: Somaia Shehab-Eldeen, Tropical Medicine Department, Faculty of Medicine, Menoufia University, Yassen Abd Al Ghafar Street, Shebin El-Kom, 32511, Egypt, Tel +20 1117251523, Email
| | - Hany R Alwakeel
- Department of Hepatology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Ehab Darwiesh
- Department of Tropical Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Abdallah Essa
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
- Department of Internal Medicine, College of Medicine, King Faisal University, Al-Ahsaa, Saudi Arabia
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42
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B HDM, Guru A, Sudhakaran G, Murugan R, Arshad A, Arockiaraj J. Double‐edged sword role of shrimp miRNA explains an evolutionary language between shrimp‐pathogen interactions that unties the knot of shrimp infection. REVIEWS IN AQUACULTURE 2022; 14:578-593. [DOI: 10.1111/raq.12613] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/21/2021] [Indexed: 10/16/2023]
Abstract
AbstractShrimp production, using a small‐scale enclosed pond system, is a rapidly growing aquaculture sector, which is valued around USD 18.30 billion in 2020. Intensified shrimp culture leads to the outbreak of transmissible diseases to eventually cause a huge loss in the production process and thus the economy. Studies on microRNA (miRNA) reveal that miRNA has an influential role in the host‐pathogen interaction during an infection. Recently, shrimp miRNA has been shown to help pathogen‐like viruses for their replication and infection. Several shrimp miRNAs were reported to be involved in enhancing host immunity against viral infection, especially white spot syndrome virus (WSSV) infection and Vibrio infection caused by bacterial species, whereas some shrimp miRNAs were reported to be hijacked by WSSV and to enhance the viral replication and establish the infection in shrimp. This gives an insight into the double‐edged sword role played by shrimp miRNA during host‐pathogen interaction. In future, this role could be employed against the virus to strengthen the shrimp culture. In this review, we discuss the role of shrimp miRNA and their mechanism(s) associated with the establishment of host‐pathogen interaction during infection, which will reveal the complexity associated with shrimp infection.
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Affiliation(s)
- Hari Deva Muthu B
- SRM Research Institute SRM Institute of Science and Technology Chennai Tamil Nadu India
- Department of Biotechnology, College of Science and Humanities SRM Institute of Science and Technology Chennai Tamil Nadu India
| | - Ajay Guru
- SRM Research Institute SRM Institute of Science and Technology Chennai Tamil Nadu India
- Department of Biotechnology, College of Science and Humanities SRM Institute of Science and Technology Chennai Tamil Nadu India
| | - Gokul Sudhakaran
- SRM Research Institute SRM Institute of Science and Technology Chennai Tamil Nadu India
- Department of Biotechnology, College of Science and Humanities SRM Institute of Science and Technology Chennai Tamil Nadu India
| | - Raghul Murugan
- SRM Research Institute SRM Institute of Science and Technology Chennai Tamil Nadu India
- Department of Biotechnology, College of Science and Humanities SRM Institute of Science and Technology Chennai Tamil Nadu India
| | - Aziz Arshad
- International Institute of Aquaculture and Aquatic Sciences (I‐AQUAS), Universiti Putra Malaysia Negeri Sembilan Malaysia
- Department of Aquaculture, Faculty of Agriculture Universiti Putra Malaysia Serdang Selangor Malaysia
| | - Jesu Arockiaraj
- SRM Research Institute SRM Institute of Science and Technology Chennai Tamil Nadu India
- Department of Biotechnology, College of Science and Humanities SRM Institute of Science and Technology Chennai Tamil Nadu India
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Zhao H, Yang J, Wang Q, Cui Z, Li D, Niu J, Guo Y, Zhang Q, Zhang S, Zhao Y, Wang K, Lian W, Hu G. Exosomal miRNA-328-3p targets ZO-3 and inhibits porcine epidemic diarrhea virus proliferation. Arch Virol 2022; 167:901-910. [PMID: 35147806 DOI: 10.1007/s00705-022-05364-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 12/06/2021] [Indexed: 11/02/2022]
Abstract
As essential transfer carriers for cell-to-cell communication and genetic material, exosomes carry microRNAs that participate in the regulation of various biological processes. MicroRNAs are a type of single-stranded noncoding RNA that bind to specific target gene mRNAs to degrade or inhibit their translation, thereby regulating target gene expression. Although it is known that a variety of microRNAs are involved in the viral infection process, there are few reports on specific microRNAs involved in porcine epidemic diarrhea virus (PEDV) infection. In this study, we isolated and identified exosomes in PEDV-infected Vero E6 cells. Using transcriptomics technology, we found that miRNA-328-3p was significantly downregulated in exosomes following PEDV infection. Moreover, exosomal miRNA-328-3p inhibited infection by PEDV by targeting and inhibiting tight junction protein 3 (TJP-3/ZO-3) in recipient cells. Our findings provide evidence that, after infecting cells, PEDV downregulates expression of miRNA-328-3p, and the resulting reduced inhibition of the target protein ZO-3 helps to enhance PEDV infection. These results provide new insight for understanding the regulatory mechanism of PEDV infection.
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Affiliation(s)
- Han Zhao
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
| | - Jinxin Yang
- Jilin Provincal Center for Animal Disease Control and Prevention, Changchun, 130117, Jilin, China
| | - Qian Wang
- Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China
| | - Zhanding Cui
- State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu, China
| | - Dengliang Li
- College of Veterinary Medicine, Northwest A&F University, Yangling, Xianyang, 712100, Shanxi, China
| | - Jiangting Niu
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
| | - Yanbing Guo
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
| | - Qian Zhang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
| | - Shuang Zhang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
| | - Yanli Zhao
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China
| | - Kai Wang
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China.
| | - Wei Lian
- Jilin ZhengYe Biological Products Co., Ltd., Jilin, 132101, Jilin, China.
| | - Guixue Hu
- College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China.
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Fernández-Pato A, Virseda-Berdices A, Resino S, Ryan P, Martínez-González O, Peréz-García F, Martin-Vicente M, Valle-Millares D, Brochado-Kith O, Blancas R, Martínez A, Ceballos FC, Bartolome-Sánchez S, Vidal-Alcántara EJ, Alonso D, Blanca-López N, Martinez-Acitores IR, Martin-Pedraza L, Jiménez-Sousa MÁ, Fernández-Rodríguez A. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. Emerg Microbes Infect 2022; 11:676-688. [PMID: 35130828 PMCID: PMC8890551 DOI: 10.1080/22221751.2022.2038021] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival. METHODS AND RESULTS Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio=4.60; p-value<0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC=0.970 vs. 0.881; p=0.042). CONCLUSIONS SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.
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Affiliation(s)
- Asier Fernández-Pato
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain.,Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Ana Virseda-Berdices
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Salvador Resino
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Pablo Ryan
- Department of Infectious Diseases, Hospital Universitario Infanta Leonor, Madrid, Spain.,School of Medicine, Complutense University of Madrid, Madrid, Spain.,Gregorio Marañón Health Research Institute, Madrid, Spain
| | | | - Felipe Peréz-García
- Clinical Microbiology Department, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain
| | - María Martin-Vicente
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Daniel Valle-Millares
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Oscar Brochado-Kith
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Rafael Blancas
- Critical Care Department, Hospital Universitario del Tajo, Aranjuez, Spain
| | - Amalia Martínez
- Department of Infectious Diseases, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Francisco C Ceballos
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Sofía Bartolome-Sánchez
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Erick Joan Vidal-Alcántara
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - David Alonso
- Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain
| | | | | | - Laura Martin-Pedraza
- Department of Infectious Diseases, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - María Ángeles Jiménez-Sousa
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Unit of Viral Infection and Immunity, National Center for Microbiology CNM, Health Institute Carlos III ISCIII, Majadahonda, Madrid, Spain
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Sui N, Zhang R, Jiang Y, Yu H, Xu G, Wang J, Zhu Y, Xie Z, Hu J, Jiang S. Integrated miRNA and mRNA Expression Profiles Reveal Differentially Expressed miR-222a as an Antiviral Factor Against Duck Hepatitis A Virus Type 1 Infection. Front Cell Infect Microbiol 2022; 11:811556. [PMID: 35047423 PMCID: PMC8761743 DOI: 10.3389/fcimb.2021.811556] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/06/2021] [Indexed: 12/11/2022] Open
Abstract
Duck hepatitis A virus 1 (DHAV-1) is a highly contagious etiological agent that causes acute hepatitis in young ducklings. MicroRNAs (miRNAs) play important regulatory roles in response to pathogens. However, the interplay between DHAV-1 infection and miRNAs remains ambiguous. We characterized and compared miRNA and mRNA expression profiles in duck embryo fibroblasts cells (DEFs) infected with DHAV-1. In total, 36 and 96 differentially expressed (DE) miRNAs, and 4110 and 2595 DE mRNAs, were identified at 12 and 24 h after infection. In particular, 126 and 275 miRNA-mRNA pairs with a negative correlation were chosen to construct an interaction network. Subsequently, we identified the functional annotation of DE mRNAs and target genes of DE miRNAs enriched in diverse Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may be important for virus resistance, cell proliferation, and metabolism. Moreover, upregulated miR-222a could negatively regulate DHAV-1 replication in DEFs and downregulate integrin subunit beta 3 (ITGB3) expression by targeting the 3' untranslated region (3'UTR), indicating that miR-222a may modulate DHAV-1 replication via interaction with ITGB3. In conclusion, the results reveal changes of mRNAs and miRNAs during DHAV-1 infection and suggest miR-222a as an antiviral factor against DHAV-1.
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Affiliation(s)
- Nana Sui
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Ruihua Zhang
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Yue Jiang
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Honglei Yu
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Guige Xu
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Jingyu Wang
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Yanli Zhu
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Zhijing Xie
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
| | - Jiaqing Hu
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China.,Shandong GreenBlue Biotechnology Co. Ltd. Economic Development Zone, Ningyang County, Taian, China
| | - Shijin Jiang
- College of Veterinary Medicine, Shandong Agricultural University, Taian, China.,Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, China
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Valacchi G, Pambianchi E, Coco S, Pulliero A, Izzotti A. MicroRNA Alterations Induced in Human Skin by Diesel Fumes, Ozone, and UV Radiation. J Pers Med 2022; 12:176. [PMID: 35207665 PMCID: PMC8880698 DOI: 10.3390/jpm12020176] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/21/2022] [Accepted: 01/24/2022] [Indexed: 11/17/2022] Open
Abstract
Epigenetic alterations are a driving force of the carcinogenesis process. MicroRNAs play a role in silencing mutated oncogenes, thus defending the cell against the adverse consequences of genotoxic damages induced by environmental pollutants. These processes have been well investigated in lungs; however, although skin is directly exposed to a great variety of environmental pollutants, more research is needed to better understand the effect on cutaneous tissue. Therefore, we investigated microRNA alteration in human skin biopsies exposed to diesel fumes, ozone, and UV light for over 24 h of exposure. UV and ozone-induced microRNA alteration right after exposure, while the peak of their deregulations induced by diesel fumes was reached only at the end of the 24 h. Diesel fumes mainly altered microRNAs involved in the carcinogenesis process, ozone in apoptosis, and UV in DNA repair. Accordingly, each tested pollutant induced a specific pattern of microRNA alteration in skin related to the intrinsic mechanisms activated by the specific pollutant. These alterations, over a short time basis, reflect adaptive events aimed at defending the tissue against damages. Conversely, whenever environmental exposure lasts for a long time, the irreversible alteration of the microRNA machinery results in epigenetic damage contributing to the pathogenesis of inflammation, dysplasia, and cancer induced by environmental pollutants.
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Affiliation(s)
- Giuseppe Valacchi
- Animal Science Department, Plants for Human Health Institute, North Carolina State University, Research Campus Kannapolis, Kannapolis, NC 28081, USA; (G.V.); (E.P.)
- Department of Environmental Sciences and Prevention, University of Ferrara, 44121 Ferrara, Italy
- Department of Food and Nutrition, Kyung Hee University, Seoul 130-701, Korea
| | - Erika Pambianchi
- Animal Science Department, Plants for Human Health Institute, North Carolina State University, Research Campus Kannapolis, Kannapolis, NC 28081, USA; (G.V.); (E.P.)
| | - Simona Coco
- Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy;
| | | | - Alberto Izzotti
- Department of Experimental Medicine, University of Genova, 16132 Genova, Italy
- UOC Mutagenesis and Cancer Prevention, IRCCS San Martino Hospital, 16132 Genova, Italy
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47
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Majumdar A, Basu A. Involvement of host microRNAs in flavivirus-induced neuropathology: An update. J Biosci 2022; 47:54. [PMID: 36222134 PMCID: PMC9425815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 04/17/2022] [Indexed: 09/07/2024]
Abstract
Flaviviruses are a spectrum of vector-borne RNA viruses that cause potentially severe diseases in humans including encephalitis, acute-flaccid paralysis, cognitive disorders and foetal abnormalities. Japanese encephalitis virus (JEV), Zika virus (ZIKV), West Nile virus (WNV) and Dengue virus (DENV) are globally emerging pathogens that lead to epidemics and outbreaks with continued transmission to newer geographical areas over time. In the past decade, studies have focussed on understanding the pathogenic mechanisms of these viruses in a bid to alleviate their disease burden. MicroRNAs (miRNAs) are short single-stranded RNAs that have emerged as master-regulators of cellular gene expression. The dynamics of miRNAs within a cell have the capacity to modulate hundreds of genes and, consequently, their physiological manifestation. Increasing evidence suggests their role in host response to disease and infection including cell survival, intracellular viral replication and immune activation. In this review, we aim to comprehensively update published evidence on the role of miRNAs in host cells infected with the common neurotropic flaviviruses, with an increased focus on neuropathogenic mechanisms. In addition, we briefly cover therapeutic advancements made in the context of miRNA-based antiviral strategies.
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Affiliation(s)
- Atreye Majumdar
- National Brain Research Centre, Manesar, Gurugram 122 052 India
| | - Anirban Basu
- National Brain Research Centre, Manesar, Gurugram 122 052 India
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Abstract
There are strong incentives for human populations to develop antiviral systems. Similarly, genomes that encode antiviral systems have had strong selective advantages. Protein-guided immune systems, which have been well studied in mammals, are necessary for survival in our virus-laden environments. Small RNA–directed antiviral immune systems suppress invasion of cells by non-self genetic material via complementary base pairing with target sequences. These RNA silencing-dependent systems operate in diverse organisms. In mammals, there is strong evidence that microRNAs (miRNAs) regulate endogenous genes important for antiviral immunity, and emerging evidence that virus-derived nucleic acids can be directly targeted by small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNAs (tRNAs) for protection in some contexts. In this review, we summarize current knowledge of the antiviral functions of each of these small RNA types and consider their conceptual and mechanistic overlap with innate and adaptive protein-guided immunity, including mammalian antiviral cytokines, as well as the prokaryotic RNA-guided immune system, CRISPR. In light of recent successes in delivery of RNA for antiviral purposes, most notably for vaccination, we discuss the potential for development of small noncoding RNA–directed antiviral therapeutics and prophylactics. Viruses are all around us and are likely inside some of the reader’s cells at this moment. Organisms are accommodated to this reality and encode various immune systems to limit virus replication. In mammals, the best studied immune systems are directed by proteins that specifically recognize viruses. These include diverse antibodies and T cell receptors, which recognize viral proteins, and pattern recognition receptors, some of which can recognize viral nucleic acids. In other organisms, including bacteria, immune systems directed by small RNAs are also well known; spacer-derived guide RNAs in CRISPR/Cas immune systems are one prominent example. The small RNAs directing these systems derive their specificity via complementary base pairing with their targets, which include both host and viral nucleic acids. Rather than having “traded in” these systems for more advanced protein-directed systems, increasing evidence supports the perspective that small RNA–directed immune systems remain active in mammalian antiviral immunity in some contexts. Here, we review what is known so far about the emerging roles of mammalian siRNAs, miRNAs, piRNAs, and tRNAs in directing immunity to viruses.
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Affiliation(s)
- Tomoko Takahashi
- Department of Biochemistry and Molecular Biology, Graduate School of Science and Engineering, Saitama University, Saitama, Japan
- * E-mail: (TT); (NFP)
| | - Steven M. Heaton
- Genome Immunobiology RIKEN Hakubi Research Team, Cluster for Pioneering Research, RIKEN, Yokohama, Japan
- Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan
| | - Nicholas F. Parrish
- Genome Immunobiology RIKEN Hakubi Research Team, Cluster for Pioneering Research, RIKEN, Yokohama, Japan
- Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan
- * E-mail: (TT); (NFP)
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Wu J, Liu X, Shao J, Zhang Y, Lu R, Xue H, Xu Y, Wang L, Zhou H, Yu L, Yue M, Dong C. Expression of plasma IFN signaling-related miRNAs during acute SARS-CoV-2 infection and its association with RBD-IgG antibody response. Virol J 2021; 18:244. [PMID: 34876159 PMCID: PMC8649682 DOI: 10.1186/s12985-021-01717-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 11/27/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a huge challenge worldwide. Although previous studies have suggested that type I interferon (IFN-I) could inhibit the virus replication, the expression characteristics of IFN-I signaling-related miRNAs (ISR-miRNAs) during acute severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and its relationship with receptor-binding domain (RBD) IgG antibody response at the recovery phase remain unclear. METHODS Expression profiles of 12 plasma ISR-miRNAs in COVID-19 patients and healthy controls were analyzed using RT-qPCR. The level of RBD-IgG antibody was determined using the competitive ELISA. Spearman correlation was done to measure the associations of plasma ISR-miRNAs with clinical characteristics during acute SARS-CoV-2 infection and RBD-IgG antibody response at the recovery phase. RESULTS Compared with the healthy controls, COVID-19 patients exhibited higher levels of miR-29b-3p (Z = 3.15, P = 0.002) and miR-1246 (Z = 4.98, P < 0.001). However, the expression of miR-186-5p and miR-15a-5p were significantly decreased. As the results shown, miR-30b-5p was negatively correlated with CD4 + T cell counts (r = - 0.41, P = 0.027) and marginally positively correlated with fasting plasma glucose in COVID-19 patients (r = 0.37, P = 0.052). The competitive ELISA analysis showed the plasma level of miR-497-5p at the acute phase was positively correlated with RBD-IgG antibody response (r = 0.48, P = 0.038). CONCLUSIONS Our present results suggested that the expression level of ISR-miRNAs was not only associated with acute SARS-CoV-2 infection but also with RBD-IgG antibody response at the recovery phase of COVID-19. Future studies should be performed to explore the biological significance of ISR-miRNAs in SARS-CoV-2 infection.
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Affiliation(s)
- Jing Wu
- Department of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, Soochow, China
| | - Xingxiang Liu
- Department of Clinical Laboratory, Huai'an Fourth People's Hospital, Huai'an, China
| | | | - Yuanyuan Zhang
- Department of Clinical Laboratory, Huai'an Fourth People's Hospital, Huai'an, China
| | - Renfei Lu
- Nantong Third People's Hospital, Nantong, China
| | - Hong Xue
- Nantong Third People's Hospital, Nantong, China
| | - Yunfang Xu
- Department of Clinical Laboratory, Huai'an Fourth People's Hospital, Huai'an, China
| | - Lijuan Wang
- Department of Clinical Laboratory, Huai'an Fourth People's Hospital, Huai'an, China
| | - Hui Zhou
- Suzhou Industrial Park Centers for Disease Control and Prevention, Soochow, China
| | - Lugang Yu
- Suzhou Industrial Park Centers for Disease Control and Prevention, Soochow, China
| | - Ming Yue
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
| | - Chen Dong
- Department of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, Soochow, China.
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50
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Sandstedt J, Vukusic K, Rekabdar E, Dellgren G, Jeppsson A, Mattsson Hultén L, Rotter Sopasakis V. Markedly reduced myocardial expression of γ-protocadherins and long non-coding RNAs in patients with heart disease. Int J Cardiol 2021; 344:149-159. [PMID: 34592247 DOI: 10.1016/j.ijcard.2021.09.046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 09/16/2021] [Accepted: 09/22/2021] [Indexed: 01/04/2023]
Abstract
BACKGROUND Adverse cardiac remodeling and tissue damage following heart disease is strongly associated with chronic low grade inflammation. The mechanisms underlying persisting inflammatory signals are not fully understood, but may involve defective and/or non-responsive transcriptional and post-transcriptional regulatory mechanisms. In the current study, we aimed to identify novel mediators and pathways involved in processes associated with inflammation in the development and maintenance of cardiac disease. METHODS AND RESULTS We performed RNA sequencing analysis of cardiac tissue from patients undergoing coronary artery bypass grafting (CABG) or aortic valve replacement (AVR) and compared with control tissue from multi-organ donors. Our results confirmed previous findings of a marked upregulated inflammatory state, but more importantly, we found pronounced reduction of non-protein coding genes, particularly long non-coding RNAs (lncRNA), including several lncRNAs known to be associated with inflammation and/or cardiovascular disease. In addition, Gene Set Enrichment Analysis revealed markedly downregulated microRNA pathways, resulting in aberrant expression of other genes, particularly γ-protocadherins. CONCLUSIONS Our data suggest that aberrant expression of non-coding gene regulators comprise crucial keys in the progression of heart disease, and may be pivotal for chronic low grade inflammation associated with cardiac dysfunction. By unmasking atypical γ-protocadherin expression as a prospective genetic biomarker of myocardial dysfunction, our study provides new insight into the complex molecular framework of heart disease. Creating new approaches to modify non-coding gene regulators, such as those identified in the current study, may define novel strategies to shift γ-protocadherin expression, thereby normalizing part of the molecular architecture associated with heart disease.
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Affiliation(s)
- Joakim Sandstedt
- Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Kristina Vukusic
- Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Elham Rekabdar
- Genomics Core Facility, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden
| | - Göran Dellgren
- Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Anders Jeppsson
- Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Lillemor Mattsson Hultén
- Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
| | - Victoria Rotter Sopasakis
- Department of Clinical Chemistry, Sahlgrenska University Hospital and Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
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