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Wang Y, Sanghvi G, Ballal S, Sharma R, Pathak PK, Shankhyan A, Sun J, Chen Q, Ma Y, Huang L, Liu Y. Molecular mechanisms of lncRNA NEAT1 in the pathogenesis of liver-related diseases, with special focus on therapeutic approaches. Pathol Res Pract 2025; 269:155867. [PMID: 40054160 DOI: 10.1016/j.prp.2025.155867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 01/13/2025] [Accepted: 02/25/2025] [Indexed: 04/19/2025]
Abstract
Liver diseases are a major worldwide health concern, with high rates of dysfunction and mortality. In recent years, a variety of lncRNAs have been studied and discovered to be engaged in numerous cellular-level regulatory mechanisms as competing endogenous RNAs (ceRNAs), which play a significant role in the development of liver-related diseases. A class of RNA molecules known as lncRNAs, which are over 200 nucleotides long, do not translate into proteins. Nuclear Enriched Abundant Transcript 1 (NEAT1) is a type of lncRNA that has a critical function in paraspeckles formation and stability. NEAT1 levels are consistently found to be higher than normal in a number of different types of diseases, as well as patients who have high levels of NEAT1 expression often have a poor prognosis. The significance and mode of action of NEAT1 in liver illnesses, such as nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ALD), liver fibrosis/cirrhosis, hepatocellular carcinoma (HCC), viral hepatitis, and liver injury, are becoming more widely known. In this review, we highlighted significant recent studies concerning the various roles of lncRNA NEAT1 in hepatic diseases. As well as, we reviewed novel therapeutic potential of lncRNAs in several liver-related diseases.
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Affiliation(s)
- Yahui Wang
- School of Medical Technology, Beijing Institute of Technology, Beijing 100081, China.
| | - Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science Marwadi University, Rajkot, Gujarat 360003, India
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Rsk Sharma
- Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh 531162, India
| | - Piyus Kumar Pathak
- Department of Applied Sciences-Chemistry, NIMS Institute of Engineering & Technology, NIMS University Rajasthan, Jaipur, India
| | - Aman Shankhyan
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab 140401, India
| | - Jiaxuan Sun
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130061, China
| | - Qingmin Chen
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130061, China
| | - Yu Ma
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130061, China
| | - Lei Huang
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130061, China
| | - Yahui Liu
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun 130061, China.
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Yonis N, Mousa A, Yousef MH, Ghouneimy AM, Dabbish AM, Abdelzaher H, Hussein MA, Ezzeldin S, Adel AA, Mahmoud YH, El-Khazragy N, Abdelnaser A. Cracking the code: lncRNA-miRNA-mRNA integrated network analysis unveiling lncRNAs as promising non-invasive NAFLD biomarkers toward precision diagnosis. Comput Biol Chem 2025; 115:108325. [PMID: 39832417 DOI: 10.1016/j.compbiolchem.2024.108325] [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: 11/13/2024] [Revised: 12/15/2024] [Accepted: 12/22/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) involves abnormal fat accumulation in the liver, mainly as triglycerides. It ranges from steatosis to non-alcoholic steatohepatitis (NASH), which can lead to inflammation, cellular damage, liver fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are crucial for regulating gene expression across various conditions. LncRNAs are emerging as potential putative diagnostic markers for NAFLD-associated HCC. METHODS We used two human and two mouse datasets from the Gene Expression Omnibus to analyze the expression profiles of mRNAs and lncRNAs. We created a network linking lncRNAs, miRNAs, and mRNAs to investigate the relationships among these RNA types. Additionally, we identified NAFLD-related lncRNAs from existing literature. We then quantified the expression levels of four specific lncRNAs, including PVT1, DUBR, SNHG17, and SNHG14, in the serum of 92 Egyptian participants using qPCR. Finally, we performed a Receiver Operating Characteristic analysis to evaluate the diagnostic potential of the candidate lncRNAs. RESULTS Our data suggests that maternally expressed gene 3 (MEG3), H19, and DPPA2 Upstream Binding RNA (DUBR) were significantly upregulated, and plasmacytoma variant translocation 1 (PVT1) was markedly downregulated. PVT1 showed the highest diagnostic accuracy for both NAFLD and NASH. The combined panels of PVT1 +H19 for NAFLD and PVT1 +H19 +DUBR for NASH demonstrated high diagnostic potential. Uniquely, PVT1 can distinguish between NAFLD and NASH. PVT1 exhibited strong diagnostic potential for NAFLD and NASH, individually and in combination with other lncRNAs. CONCLUSION Our study identifies four lncRNAs as putative biomarkers with high specificity and accuracy, individually or combined, for differentiating between NAFLD and NASH. Healthy volunteers with PVT1 possess the highest diagnostic accuracy and significantly discriminate between NAFLD and NASH.
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Affiliation(s)
- Nouran Yonis
- Institute of Global Health and Human Ecology (IGHHE), School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Ahmed Mousa
- University of Science and Technology, Zewail City of Science and Technology, Giza, Egypt
| | - Mohamed H Yousef
- Biotechnology Graduate Program, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Ahmed M Ghouneimy
- Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Areeg M Dabbish
- Biotechnology Graduate Program, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Hana Abdelzaher
- Institute of Global Health and Human Ecology (IGHHE), School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Mohamed Ali Hussein
- Institute of Global Health and Human Ecology (IGHHE), School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt
| | - Shahd Ezzeldin
- Basic Research Department, Proteomics and Metabolomics Research Program, Children's Cancer Hospital 57357 (CCHE-57357), Cairo, Egypt
| | - Abdelmoneim A Adel
- Hematology and Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Egypt
| | - Yosra H Mahmoud
- Hematology and Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Egypt
| | - Nashwa El-Khazragy
- Clinical Pathology and Hematology Department, Faculty of Medicine, Ain Shams University Biomedical Research Department, Cairo 11381, Egypt
| | - Anwar Abdelnaser
- Institute of Global Health and Human Ecology (IGHHE), School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt.
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Chen Y, Bian S, Le J. Molecular Landscape and Diagnostic Model of MASH: Transcriptomic, Proteomic, Metabolomic, and Lipidomic Perspectives. Genes (Basel) 2025; 16:399. [PMID: 40282358 PMCID: PMC12026639 DOI: 10.3390/genes16040399] [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: 02/19/2025] [Revised: 03/26/2025] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of fatty liver disease, presents a significant global health challenge. Despite extensive research, fully elucidating its complex pathogenesis and developing accurate non-invasive diagnostic tools remain key goals. Multi-omics approaches, integrating data from transcriptomics, proteomics, metabolomics, and lipidomics, offer a powerful strategy to achieve these aims. This review summarizes key findings from multi-omics studies in MASH, highlighting their contributions to our understanding of disease mechanisms and the development of improved diagnostic models. Transcriptomic studies have revealed widespread gene dysregulation affecting lipid metabolism, inflammation, and fibrosis, while proteomics has identified altered protein expression patterns and potential biomarkers. Metabolomic and lipidomic analyses have further uncovered significant changes in various metabolites and lipid species, including ceramides, sphingomyelins, phospholipids, and bile acids, underscoring the central role of lipid dysregulation in MASH. These multi-omics findings have been leveraged to develop novel diagnostic models, some incorporating machine learning algorithms, with improved accuracy compared to traditional methods. Further research is needed to validate these findings, explore the complex interplay between different omics layers, and translate these discoveries into clinically useful tools for improved MASH diagnosis and prognosis.
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Affiliation(s)
- Yilong Chen
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (Y.C.); (S.B.)
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
| | - Shuixiu Bian
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (Y.C.); (S.B.)
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
| | - Jiamei Le
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (Y.C.); (S.B.)
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
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Soltanieh SK, Khastar S, Kaur I, Kumar A, Bansal J, Fateh A, Nathiya D, Husseen B, Rajabivahid M, Dehghani-Ghorbi M, Akhavan-Sigari R. Long Non-Coding RNAs in Non-Alcoholic Fatty Liver Disease; Friends or Foes? Cell Biochem Biophys 2025; 83:279-294. [PMID: 39377981 DOI: 10.1007/s12013-024-01555-8] [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] [Accepted: 09/17/2024] [Indexed: 01/03/2025]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a range of conditions that start with the accumulation of fat in the liver (hepatic steatosis) and can progress to more severe stages like steatohepatitis (NASH) and fibrosis without drinking alcohol. Environmental and genetic variables both contribute to MAFLD's development, with various biological processes and mediators involved at every phase. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that are not translated into protein and are over 200 nucleotides long. They can impact genes that encode protein by controlling transcriptional and post-transcriptional procedures. Dysregulation of lncRNA has been connected to several liver diseases, including MAFLD. Recent research has linked lncRNAs to MAFLD pathology in both patients and animal models. However, the roles of most lncRNAs in MAFLD pathology are still not well recognized. This review provides a comprehensive catalog of recently reported lncRNAs in the pathogenesis of MAFLD and summarizes the current knowledge of lncRNAs usage as therapeutic strategies in MAFLD, the most common liver disease. Collectively, lncRNA's targeting could potentially offer a therapeutic approach by modulating MAFLD.
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Affiliation(s)
| | - Sahar Khastar
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Irwanjot Kaur
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka-560069, India
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan-303012, India
| | - Abhishek Kumar
- School of Pharmacy-Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Gangoh, Uttar Pradesh-247341, India
- Department of Pharmacy, Arka Jain University, Jamshedpur, Jharkhand-831001, India
| | - Jaya Bansal
- Department of Applied Sciences, Chandigarh Engineering College, Chandigarh Group of Colleges, Jhanjeri, Mohali, 140307, Punjab, India
| | - Ata Fateh
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Deepak Nathiya
- Department of Pharmacy Practice, Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | - Beneen Husseen
- Medical Laboratory Technique College, the Islamic University, Najaf, Iraq
- Medical Laboratory Technique College, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
| | - Mansour Rajabivahid
- Department of Internal Medicine, Valiasr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Mahmoud Dehghani-Ghorbi
- Hematology-Oncology Department, Imam Hossein Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Reza Akhavan-Sigari
- Department of Neurosurgery, University Medical Center Tuebingen, Tuebingen, Germany
- Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Warszawa, Poland
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5
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Li W, Xu G, Chai GW, Ball A, Zhang Q, Kutryk MJB. The MiR-139-5p and CXCR4 axis may play a role in high glucose-induced inflammation by regulating monocyte migration. Sci Rep 2025; 15:6738. [PMID: 40000897 PMCID: PMC11861593 DOI: 10.1038/s41598-025-91100-1] [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: 10/03/2024] [Accepted: 02/18/2025] [Indexed: 02/27/2025] Open
Abstract
MicroRNAs, a class of small non-coding RNA molecules that regulate gene expression post-transcriptionally, are implicated in various pathological conditions including diabetes mellitus (DM). DM has been increasingly recognized as an inflammatory disease and monocytes play a key role in propagating inflammation under hyperglycemic conditions. We hypothesize that high glucose dysregulates microRNAs to promote monocyte inflammatory activity, which may contribute to the pathogenesis of DM. THP-1 monocytes were cultured in normal (5 mM) and high (25 mM) glucose conditions. RT-qPCR and Western blotting were performed to assay microRNAs and proteins, respectively. Monocytes were transfected with microRNA mimics using Lipofectamine RNAiMAX reagent. THP-1 monocyte growth was assessed using Calcein-AM dye and a Boyden chamber assay was applied to measure monocyte migration. The results showed that high glucose downregulated miR-139-5p associated with increased protein expression of CXCR4, an experimentally validated target of miR-139-5p. Correspondingly, treatment with high glucose resulted in a significant increase in THP-1 cell migration towards SDF-1, a cognate ligand for CXCR4. MiR-139-5p overexpression inhibited high glucose-induced CXCR4 expression, leading to reduced cell migration towards SDF-1. High glucose did not affect THP-1 monocyte growth. In conclusion, the miR-139-5p-CXCR4 axis may play a role in high glucose-induced inflammation by regulating monocyte migration.
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Affiliation(s)
- Weifang Li
- Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada
| | - Gengchen Xu
- Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada
| | - Gregory W Chai
- Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada
| | - Alexander Ball
- Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada
| | - Qiuwang Zhang
- Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
| | - Michael J B Kutryk
- Division of Cardiology, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
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Bourganou MV, Chondrogianni ME, Kyrou I, Flessa CM, Chatzigeorgiou A, Oikonomou E, Lambadiari V, Randeva HS, Kassi E. Unraveling Metabolic Dysfunction-Associated Steatotic Liver Disease Through the Use of Omics Technologies. Int J Mol Sci 2025; 26:1589. [PMID: 40004054 PMCID: PMC11855544 DOI: 10.3390/ijms26041589] [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: 01/05/2025] [Revised: 02/07/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is the most prevalent liver disorder globally, linked to obesity, type 2 diabetes, and cardiovascular risk. Understanding its potential progression from simple steatosis to cirrhosis and hepatocellular carcinoma (HCC) is crucial for patient management and treatment strategies. The disease's complexity requires innovative approaches for early detection and personalized care. Omics technologies-such as genomics, transcriptomics, proteomics, metabolomics, and exposomics-are revolutionizing the study of MASLD. These high-throughput techniques allow for a deeper exploration of the molecular mechanisms driving disease progression. Genomics can identify genetic predispositions, whilst transcriptomics and proteomics reveal changes in gene expression and protein profiles during disease evolution. Metabolomics offers insights into the metabolic alterations associated with MASLD, while exposomics links environmental exposures to MASLD progression and pathology. By integrating data from various omics platforms, researchers can map out the intricate biochemical pathways involved in liver disease progression. This review discusses the roles of omics technologies in enhancing the understanding of disease progression and highlights potential diagnostic and therapeutic targets within the MASLD spectrum, emphasizing the need for non-invasive tools in disease staging and treatment development.
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Affiliation(s)
- Maria V. Bourganou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
| | - Maria Eleni Chondrogianni
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
- Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Ioannis Kyrou
- Laboratory of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, School of Food and Nutritional Sciences, Agricultural University of Athens, 11855 Athens, Greece
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Centre for Health & Life Sciences, Coventry University, Coventry CV1 5FB, UK
- Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK
- College of Health, Psychology and Social Care, University of Derby, Derby DE22 IGB, UK
| | - Christina-Maria Flessa
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
| | - Antonios Chatzigeorgiou
- Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece;
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, “Sotiria” Thoracic Diseases Hospital of Athens, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Vaia Lambadiari
- 2nd Department of Internal-Medicine, Diabetes Centre, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Harpal S. Randeva
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Centre for Health & Life Sciences, Coventry University, Coventry CV1 5FB, UK
| | - Eva Kassi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.V.B.); (M.E.C.); (C.-M.F.)
- Endocrine Unit, 1st Department of Propaedeutic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
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7
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Lu C, Han M, Ma Q, Ying L, Zhang Y. Identification of biomarkers associated with coronary artery disease and non-alcoholic fatty liver disease by bioinformatics analysis and machine learning. Sci Rep 2025; 15:3557. [PMID: 39875572 PMCID: PMC11775188 DOI: 10.1038/s41598-025-87923-7] [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: 04/08/2024] [Accepted: 01/22/2025] [Indexed: 01/30/2025] Open
Abstract
The constantly emerging evidence indicates a close association between coronary artery disease (CAD) and non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms underlying their mutual relationship remain undefined. This study aims to explore the common signature genes, potential mechanisms, diagnostic markers, and therapeutic targets for CAD and NAFLD. We downloaded CAD and NAFLD datasets from the Gene Expression Omnibus (GEO) database and analyzed the differentially expressed genes (DEGs) by limma. Protein-protein interaction (PPI) network was constructed with common DEGs (co-DEGs), and hub genes were screened by Maximal Clique Centrality (MCC) algorithm. Candidate biomarkers were selected from intersection of three machine learning algorithms. Expression levels, nomogram, the areas under the receiver operating characteristic curve (AUC) of candidate biomarkers were performed. CIBERSORT algorithm was used to assess the immune cell infiltration, and Spearman's correlations tests were used for calculating the correlation of biomarker genes. A total of 554 overlapping DEGs associated with CAD and NAFLD were obtained by analysis of GSE113079 and GSE89632 datasets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the co-DEGs were significantly enriched in immune effector process, inflammation response and lipid metabolism. The PPI network generated a 1245-edge network, and top 50 genes were selected using the MCC algorithm. The candidate biomarkers were screened from intersection of machine learning in GSE89632, including CEBPA, CXCL2, JUN and FOXO1. The ROC results showed that these four biomarker genes have good diagnostic value for patients with both CAD and NAFLD. Then we explored the immune landscape, immune infiltration and the correlation between biomarker gene expression in CAD and NAFLD samples. In this study, we predict that CEBPA, CXCL2, JUN and FOXO1 can be used to diagnose CAD and NAFLD. Our study provided new insights for potential biomarkers, molecular mechanism and therapeutic targets for both diseases.
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Affiliation(s)
- Chuan Lu
- Department of Cardiology, the Second Hospital of Dalian Medical University, Dalian, 116021, China
| | - Mei Han
- Department of Gastroenterology, the Second Hospital of Dalian Medical University, Dalian, 116021, China
| | - Qiqi Ma
- Department of Gastroenterology, the Second Hospital of Dalian Medical University, Dalian, 116021, China
| | - Li Ying
- Department of Gastroenterology, the Second Hospital of Dalian Medical University, Dalian, 116021, China.
| | - Yue Zhang
- Department of Gastroenterology, the Second Hospital of Dalian Medical University, Dalian, 116021, China.
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8
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Wade H, Pan K, Zhang B, Zheng W, Su Q. Mechanistic role of long non-coding RNAs in the pathogenesis of metabolic dysfunction-associated steatotic liver disease and fibrosis. EGASTROENTEROLOGY 2024; 2:e100115. [PMID: 39872125 PMCID: PMC11729351 DOI: 10.1136/egastro-2024-100115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/29/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease, encompasses a broad range of hepatic metabolic disorders primarily characterised by the disruption of hepatic lipid metabolism, hepatic lipid accumulation and steatosis. Severe cases of MASLD might progress to metabolic dysfunction-associated steatohepatitis, characterised by hepatic inflammation, hepatocyte ballooning degeneration, activation of hepatic stellate cells (HSCs) and fibrogenesis. It may further progress to hepatocellular carcinoma. In the liver, long non-coding RNAs (lncRNAs) target multiple metabolic pathways in hepatocytes, HSCs, and Kupffer cells at different stages of MASLD and liver fibrosis. In this study, we overview recent findings on the potential role of lncRNAs in the pathogenesis of MASLD and liver fibrosis via modulation of de novo lipid synthesis, fatty acid β-oxidation, lipotoxicity, oxidative stress, metabolic inflammation, mammalian target of rapamycin signalling, apoptosis, ubiquitination and fibrogenesis. We critically assess the literature reports that investigate the complex interplay between lncRNA, microRNA and key mediators in liver injury, in both human participants and animal models of MASLD and liver fibrosis. We also highlight the therapeutic potential of lncRNAs in chronic liver diseases.
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Affiliation(s)
- Henry Wade
- School of Biological Sciences, Queen’s University Belfast, Belfast, UK
| | - Kaichao Pan
- Endocrinology Group, Advocate Illinois Masonic Medical Center, Chicago, Illinois, USA
| | - Bingrui Zhang
- School of Biological Sciences, Queen’s University Belfast, Belfast, UK
| | - Wenhua Zheng
- Faculty of Health Science, University of Macau, Macau, China
| | - Qiaozhu Su
- School of Biological Sciences, Queen’s University Belfast, Belfast, UK
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Xiao Q, Zhang Y, Ni H, Yin Y, Gao A, Cui B, Zhang W, Li Y, Yang Y. Core competing endogenous RNA network based on mRNA and non-coding RNA expression profiles in chicken fatty liver. Anim Genet 2024; 55:772-778. [PMID: 39164964 DOI: 10.1111/age.13469] [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: 06/27/2024] [Revised: 06/27/2024] [Accepted: 07/29/2024] [Indexed: 08/22/2024]
Abstract
Fatty liver disease is a common metabolic disease in chickens. This disease can lead to a decrease in egg production and increase the risk of death in chickens. Long non-coding RNAs (lncRNAs) are involved in fatty liver formation by directly targeting genes or regulating gene expression by competitively binding microRNAs. However, a large proportion of competing endogenous RNA (ceRNA) networks in fatty liver diseases are still unclear. The total of 300 Jingxing-Huang chickens were used for fatty liver model construction. Then, differentially expressed (DE) genes (DEGs) identified through whole-transcriptome sequencing from four chickens with fatty liver and four chickens without fatty liver were chosen from the F1 generation. A total of 953 DEGs were identified between the fatty liver group and the control group, including 26 DE micro (mi)RNAs and 56 DE lncRNAs. Differential expression heatmaps and volcano plots were obtained after clustering expression analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that these DEGs were involved in many biological processes and signaling pathways related to fatty acid metabolism and lipid synthesis. Furthermore, cytoscape was used to construct a ceRNA network of the DE miRNAs, DE mRNAs, and DE lncRNAs. Eleven DE lncRNAs, seven DE miRNAs, and 13 DE mRNAs were found to be associated with the pathogenesis of fatty liver disease. An lncRNA-miRNA-mRNA ceRNA network was constructed to elucidate the mechanisms of fatty liver diseases, and the ENSGALT00000079786-miR-140/miR-143/miR-1a/miR-22/miR-375 network was identified. These results provide a valuable resource for further elucidating the posttranscriptional regulatory mechanisms of chicken liver and adipose fat development or deposition.
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Affiliation(s)
- Qingxing Xiao
- College of Animal Science, Jilin University, Changchun, China
| | - Yonghong Zhang
- College of Animal Science, Jilin University, Changchun, China
| | - Hongyu Ni
- College of Animal Science, Jilin University, Changchun, China
| | - Yijing Yin
- College of Animal Science, Jilin University, Changchun, China
| | - Anchong Gao
- College of Animal Science, Jilin University, Changchun, China
| | - Benhai Cui
- Jiuzhou Flying Goose Husbandry & Technology Co., Ltd., Baicheng, China
| | - Wei Zhang
- Animal Disease Prevention and Control Center, Baicheng, China
| | - Yumei Li
- College of Animal Science, Jilin University, Changchun, China
| | - Yuwei Yang
- College of Animal Science, Jilin University, Changchun, China
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Yuan H, Jung ES, Chae SW, Jung SJ, Daily JW, Park S. Biomarkers for Health Functional Foods in Metabolic Dysfunction-Associated Steatotic Liver Disorder (MASLD) Prevention: An Integrative Analysis of Network Pharmacology, Gut Microbiota, and Multi-Omics. Nutrients 2024; 16:3061. [PMID: 39339660 PMCID: PMC11434757 DOI: 10.3390/nu16183061] [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: 08/07/2024] [Revised: 09/01/2024] [Accepted: 09/05/2024] [Indexed: 09/30/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disorder (MASLD) is increasingly prevalent globally, highlighting the need for preventive strategies and early interventions. This comprehensive review explores the potential of health functional foods (HFFs) to maintain healthy liver function and prevent MASLD through an integrative analysis of network pharmacology, gut microbiota, and multi-omics approaches. We first examined the biomarkers associated with MASLD, emphasizing the complex interplay of genetic, environmental, and lifestyle factors. We then applied network pharmacology to identify food components with potential beneficial effects on liver health and metabolic function, elucidating their action mechanisms. This review identifies and evaluates strategies for halting or reversing the development of steatotic liver disease in the early stages, as well as biomarkers that can evaluate the success or failure of such strategies. The crucial role of the gut microbiota and its metabolites for MASLD prevention and metabolic homeostasis is discussed. We also cover state-of-the-art omics approaches, including transcriptomics, metabolomics, and integrated multi-omics analyses, in research on preventing MASLD. These advanced technologies provide deeper insights into physiological mechanisms and potential biomarkers for HFF development. The review concludes by proposing an integrated approach for developing HFFs targeting MASLD prevention, considering the Korean regulatory framework. We outline future research directions that bridge the gap between basic science and practical applications in health functional food development. This narrative review provides a foundation for researchers and food industry professionals interested in developing HFFs to support liver health. Emphasis is placed on maintaining metabolic balance and focusing on prevention and early-stage intervention strategies.
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Affiliation(s)
- Heng Yuan
- Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea;
| | - Eun-Soo Jung
- Clinical Trial Center for Functional Foods, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (E.-S.J.); (S.-W.C.); (S.-J.J.)
- Clinical Trial Center for K-FOOD Microbiome, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
| | - Soo-Wan Chae
- Clinical Trial Center for Functional Foods, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (E.-S.J.); (S.-W.C.); (S.-J.J.)
- Clinical Trial Center for K-FOOD Microbiome, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
| | - Su-Jin Jung
- Clinical Trial Center for Functional Foods, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea; (E.-S.J.); (S.-W.C.); (S.-J.J.)
- Clinical Trial Center for K-FOOD Microbiome, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Republic of Korea
- Research Institute of Clinical Medicine, Jeonbuk National University, Jeonju 54907, Republic of Korea
| | - James W. Daily
- Department of R&D, Daily Manufacturing Inc., Rockwell, NC 28138, USA;
| | - Sunmin Park
- Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea;
- Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, 20 Hoseoro79bungil, Asan 31499, Republic of Korea
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Saleh RO, Alkhafaji AT, Mohammed JS, Bansal P, Kaur H, Ahmad I, Hjazi A, Mohammed IH, Jawad MA, Zwamel AH. LncRNA NEAT1 in the pathogenesis of liver-related diseases. Cell Biochem Funct 2024; 42:e4006. [PMID: 38622913 DOI: 10.1002/cbf.4006] [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: 02/24/2024] [Revised: 03/20/2024] [Accepted: 03/27/2024] [Indexed: 04/17/2024]
Abstract
Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long noncoding RNA (lncRNA) that is widely expressed in a variety of mammalian cell types. Altered expression levels of the lncRNA NEAT1 have been reported in liver-related disorders including cancer, fatty liver disease, liver fibrosis, viral hepatitis, and hepatic ischemia. lncRNA NEAT1 mostly acts as a competing endogenous RNA (ceRNA) to sponge various miRNAs (miRs) to regulate different functions. In regard to hepatic cancers, the elevated expression of NEAT1 has been reported to have a relation with the proliferation, migration, angiogenesis, apoptosis, as well as epithelial-mesenchymal transition (EMT) of cancer cells. Furthermore, NEAT1 upregulation has contributed to the pathogenesis of other liver diseases such as fibrosis. In this review, we summarize and discuss the molecular mechanisms by which NEAT1 contributes to liver-related disorders including acute liver failure, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and liver carcinoma, providing novel insights and introducing NEAT1 as a potential therapeutic target in these diseases.
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Affiliation(s)
- Raed Obaid Saleh
- Department of Medical Laboratory Techniques, Al-Maarif University College, Al-Anbar, Iraq
| | | | | | - Pooja Bansal
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka, India
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, India
| | - Harpreet Kaur
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh, India
- Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand, India
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | | | - Mohammed Abed Jawad
- Department of Medical Laboratories Technology, Al-Nisour University College, Baghdad, Iraq
| | - Ahmed Hussein Zwamel
- Medical laboratory technique college, the Islamic University, Najaf, Iraq
- Medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- Medical laboratory technique college, the Islamic University of Babylon, Babylon, Iraq
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12
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Zhang H, Axinbai M, Zhao Y, Wei J, Qu T, Kong J, He Y, Zhang L. Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease. Eur J Med Res 2023; 28:605. [PMID: 38115130 PMCID: PMC10729346 DOI: 10.1186/s40001-023-01457-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 10/18/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND The morbidity and mortality rates of patients with non-alcoholic fatty liver disease (NAFLD) have been steadily increasing in recent years. Previous studies have confirmed the important role of ferroptosis in NAFLD development; however, the precise mechanism through which ferroptosis influences NAFLD occurrence remains unclear. The present study aimed to identify and validate ferroptosis-related genes involved in NAFLD pathogenesis and to investigate the underlying molecular mechanisms of NAFLD. METHODS We downloaded microarray datasets GSE72756 and GSE24807 to identify differentially expressed genes (DEGs) between samples from healthy individuals and patients with NAFLD. From these DEGs, we extracted ferroptosis-related DEGs. GSE89632, another microarray dataset, was used to validate the expression of ferroptosis-related genes. A protein-protein interaction (PPI) network of ferroptosis-related genes was then constructed. The target genes were also subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, competing endogenous RNA networks were constructed. We used the CIBERSORT package to evaluate the infiltration of immune cells infiltration in NAFLD. RESULTS Five ferroptosis-related genes (SCP2, MUC1, DPP4, SLC1A4, and TF) were identified as promising diagnostic biomarkers for NAFLD. Enrichment analyses revealed that these genes are mainly involved in metabolic processes. NEAT1-miR-1224-5p-SCP2, NEAT1-miR-485-5p-MUC1, MALAT1-miR-485-5p-MUC1, and CNOT6-miR-145-5p-SLC1A4 are likely to be the potential RNA regulatory pathways that affect NAFLD development. Principal component analysis indicated significant differences in immune cell infiltration between the two groups. CONCLUSIONS This study identified five ferroptosis-related genes as potential biomarkers for diagnosing NAFLD. The correlations between the expression of ferroptosis-related genes and immune cell infiltration might shed light on the study of the molecular mechanism underlying NAFLD development.
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Affiliation(s)
- Huan Zhang
- Department of Digestion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Malina Axinbai
- Department of Digestion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
- Xinjiang Medical University, Urumqi, China
| | - Yuqing Zhao
- Beijing University of Chinese Medicine, Beijing, China
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaoyang Wei
- Department of Digestion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Tongshuo Qu
- Department of Digestion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Jingmin Kong
- Department of Emergency, Beijing Chaoyang Integrative Medicine Rescue and First Aid Hospital, Beijing, China
| | - Yongqiang He
- Department of Digestion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
| | - Liping Zhang
- Department of Digestion, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
- Beijing University of Chinese Medicine, Beijing, China.
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Dong Y, Hu M, Tan K, Dai R. ZNF143 inhibits hepatocyte mitophagy and promotes non-alcoholic fatty liver disease by targeting increased lncRNA NEAT1 expression to activate ROCK2 pathway. Epigenetics 2023; 18:2239592. [PMID: 37566742 PMCID: PMC10424604 DOI: 10.1080/15592294.2023.2239592] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 05/04/2023] [Accepted: 05/16/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorders worldwide. The mitophagy is suggested to be repressed in NAFLD, but the mechanism remains to be elucidated. METHODS NAFLD cell and mouse models were established by treating with free fatty acid (FFA) and feeding a high fat diet (HFD), respectively. QRT-PCR, Western blotting, or IHC measured the expression of ZNF143, lncRNA NEAT1, ROCK2, and lipid formation/mitophagy-related proteins. Cell viability and mitophagy were evaluated by MTT and immunofluorescence. The chloroform-methanol extraction method measured triglyceride and total cholesterol levels. ELISA detected ALT and AST levels. The interactions among ZNF143, lncRNA NEAT1 and SND1 were analysed by ChIP, dual-luciferase reporter, pull-down, and RIP. The lipid droplets were determined by Oil-red O and HE staining. RESULTS ZNF143 and lncRNA NEAT1 were upregulated in hepatic cells treated with FFA (p < 0.01 and p < 0.001). Knockdown of ZNF143 or lncRNA NEAT1 inhibited lipid droplets formation, while promoting mitophagy (p < 0.01 and p < 0.001). ZNF143 promoted lncRNA NEAT1 transcriptional expression through binding to its promoter. LncRNA NEAT1 increased ROCK2 mRNA stability by targeting SND1. LncRNA NEAT1 or ROCK2 overexpression reversed the effect of ZNF143 or lncRNA NEAT1 knockdown on hepatic steatosis and mitophagy (p < 0.01 and p < 0.001). ZNF143 or lncRNA NEAT1 knockdown inhibited HFD-induced steatosis and promoted mitophagy in vivo (p < 0.01 and p < 0.001). CONCLUSION The upregulation of lncRNA NEAT1 caused by ZNF143 promoted NAFLD through inhibiting mitophagy via activating ROCK2 pathway by targeting SND1, providing potential targets for NAFLD therapy.
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Affiliation(s)
- Yujie Dong
- The First Affiliated Hospital, Department of Ultrasound Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan421001, China
| | - Minjie Hu
- The First Affiliated Hospital, Department of Cardiothoracic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan421001, China
| | - Kewei Tan
- The No.922 Hospital of the People Liberation Army Joint Logistics Support Force, Department of the Laboratory and Blood Transfusion, Hengyang, Hunan421002, China
| | - Rongjuan Dai
- The First Affiliated Hospital, Department of Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan421001, China
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14
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Zong Y, Wang X, Cui B, Xiong X, Wu A, Lin C, Zhang Y. Decoding the regulatory roles of non-coding RNAs in cellular metabolism and disease. Mol Ther 2023; 31:1562-1576. [PMID: 37113055 PMCID: PMC10277898 DOI: 10.1016/j.ymthe.2023.04.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 04/12/2023] [Accepted: 04/21/2023] [Indexed: 04/29/2023] Open
Abstract
Non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are being studied extensively in a variety of fields. Their roles in metabolism have received increasing attention in recent years but are not yet clear. The regulation of glucose, fatty acid, and amino acid metabolism is an imperative physiological process that occurs in living organisms and takes part in cancer and cardiovascular diseases. Here, we summarize the important roles played by non-coding RNAs in glucose metabolism, fatty acid metabolism, and amino acid metabolism, as well as the mechanisms involved. We also summarize the therapeutic advances for non-coding RNAs in diseases such as obesity, cardiovascular disease, and some metabolic diseases. Overall, non-coding RNAs are indispensable factors in metabolism and have a significant role in the three major metabolisms, which may be exploited as therapeutic targets in the future.
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Affiliation(s)
- Yuru Zong
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China
| | - Xuliang Wang
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China
| | - Bing Cui
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China
| | - Xiaowei Xiong
- Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
| | - Andrew Wu
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Chunru Lin
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
| | - Yaohua Zhang
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100069, China.
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15
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Shi N, Sun K, Tang H, Mao J. The impact and role of identified long noncoding RNAs in nonalcoholic fatty liver disease: A narrative review. J Clin Lab Anal 2023; 37:e24943. [PMID: 37435630 PMCID: PMC10431402 DOI: 10.1002/jcla.24943] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 06/07/2023] [Accepted: 07/02/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, but its mechanism and pathophysiology remain unclear. Long noncoding RNAs (lncRNAs) may exert a vital influence on regulating various biological functions in NAFLD. METHODS The databases such as Google Scholar, PubMed, and Medline were searched using the following keywords: nonalcoholic fatty liver disease, nonalcoholic fatty liver disease, NAFLD, nonalcoholic steatohepatitis, nonalcoholic steatohepatitis, NASH, long noncoding RNAs, and lncRNAs. Considering the titles and abstracts, unrelated studies were excluded. The authors evaluated the full texts of the remaining studies. RESULTS We summarized the current knowledge of lncRNAs and the main signaling pathways of lncRNAs involved in NAFLD explored in recent years. As a heterogeneous group of noncoding RNAs (ncRNAs), lncRNAs play crucial roles in biological processes underlying the pathophysiology of NAFLD. The mechanisms, particularly those associated with the regulation of the expression and activities of lncRNAs, play important roles in NAFLD. CONCLUSION A better comprehension of the mechanism controlled by lncRNAs in NAFLD is necessary for the identification of novel therapeutic targets for drug development and improved, noninvasive methods for diagnosis.
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Affiliation(s)
- Na Shi
- Department of GastroenterologyFirst Affiliated Hospital of Dalian Medical UniversityDalianChina
- Department of Internal MedicineThe Third People's Hospital of ChengduChengduChina
| | - Kang Sun
- Department of GastroenterologyFirst Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Haiying Tang
- Department of Respiratory and Critical Care MedicineFirst Affiliated Hospital of Dalian Medical UniversityDalianChina
| | - Jingwei Mao
- Department of GastroenterologyFirst Affiliated Hospital of Dalian Medical UniversityDalianChina
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16
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Zeng Q, Liu CH, Wu D, Jiang W, Zhang N, Tang H. LncRNA and circRNA in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review. Biomolecules 2023; 13:biom13030560. [PMID: 36979495 PMCID: PMC10046118 DOI: 10.3390/biom13030560] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/30/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide. Early identification and prompt treatment are critical to optimize patient management and improve long-term prognosis. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are recently emerging non-coding RNAs, and are highly stable and easily detected in the circulation, representing a promising non-invasive approach for predicting NAFLD. A literature search of the Pubmed, Embase, Web of Science, and Cochrane Library databases was performed and 36 eligible studies were retrieved, including 18 on NAFLD, 13 on nonalcoholic steatohepatitis (NASH), and 11 on fibrosis and/or cirrhosis. Dynamic changes in lncRNA expression were associated with the occurrence and progression of NAFLD, among which lncRNA NEAT1, MEG3, and MALAT1 exhibited great potential as biomarkers for NAFLD. Moreover, mitochondria-located circRNA SCAR can drive metaflammation and its inhibition might be a promising therapeutic target for NASH. In this systematic review, we highlight the great potential of lncRNA/circRNA for early diagnosis and progression assessment of NAFLD. To further verify their clinical value, large-cohort studies incorporating lncRNA and circRNA expression both in liver tissue and blood should be conducted. Additionally, detailed studies on the functional mechanisms of NEAT1, MEG3, and MALAT1 will be essential for elucidating their roles in diagnosing and treating NAFLD, NASH, and fibrosis.
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Affiliation(s)
- Qingmin Zeng
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chang-Hai Liu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Dongbo Wu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wei Jiang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Nannan Zhang
- National Center for Birth Defect Monitoring, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China
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Cao L, Qu N, Wang X, Chen L, Liu M. The function of long non-coding RNA in non-alcoholic fatty liver disease. Clin Res Hepatol Gastroenterol 2023; 47:102095. [PMID: 36781069 DOI: 10.1016/j.clinre.2023.102095] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 01/24/2023] [Accepted: 02/09/2023] [Indexed: 02/15/2023]
Abstract
Non-alcoholic fatty liver disease is a disease that is currently prevalent in the world, increasingly becoming the mainstay of liver diseases. And its prevalence is rapidly increasing, but its pathogenesis is not entirely understood. Long non-coding RNAs have increasingly gained attention as science has progressed in recent years. Studies have shown that long non-coding RNAs are involved in a variety of biological processes in vivo, such as proliferation, differentiation, and apoptosis, and can affect disease by regulating gene expression. This review explores the biological processes involving long non-coding RNAs, including lipid metabolism, glucose metabolism, liver fibrosis, and apoptosis. In addition, we summarize how the different long non-coding RNAs involved in each process function. Finally, the shortcomings of long non-coding RNAs as potential therapeutic targets are briefly described. In conclusion, this article provides a clear visualization of the link that exists between long non-coding RNAs and non-alcoholic fatty liver disease.
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Affiliation(s)
- Lianrui Cao
- School of Pharmaceutical Sciences, Liaoning University, No.66, Chongshan Mid Road, Shenyang 110036, China
| | - Na Qu
- School of Pharmaceutical Sciences, Liaoning University, No.66, Chongshan Mid Road, Shenyang 110036, China
| | - Xin Wang
- School of Pharmaceutical Sciences, Liaoning University, No.66, Chongshan Mid Road, Shenyang 110036, China
| | - Lijiang Chen
- School of Pharmaceutical Sciences, Liaoning University, No.66, Chongshan Mid Road, Shenyang 110036, China.
| | - Mingxia Liu
- School of Pharmaceutical Sciences, Liaoning University, No.66, Chongshan Mid Road, Shenyang 110036, China.
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18
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Wu C, Rakhshandehroo T, Wettersten HI, Campos A, von Schalscha T, Jain S, Yu Z, Tan J, Mose E, Childers BG, Lowy AM, Weis SM, Cheresh DA. Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation. Nat Cell Biol 2023; 25:309-322. [PMID: 36646789 PMCID: PMC10280815 DOI: 10.1038/s41556-022-01055-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 11/16/2022] [Indexed: 01/18/2023]
Abstract
Defining drivers of tumour initiation can provide opportunities to control cancer progression. Here we report that lysophosphatidic acid receptor 4 (LPAR4) becomes transiently upregulated on pancreatic cancer cells exposed to environmental stress or chemotherapy where it promotes stress tolerance, drug resistance, self-renewal and tumour initiation. Pancreatic cancer cells gain LPAR4 expression in response to stress by downregulating a tumour suppressor, miR-139-5p. Even in the absence of exogenous lysophosphatidic acid, LPAR4-expressing tumour cells display an enrichment of extracellular matrix genes that are established drivers of cancer stemness. Mechanistically, upregulation of fibronectin via an LPAR4/AKT/CREB axis is indispensable for LPAR4-induced tumour initiation and stress tolerance. Moreover, ligation of this fibronectin-containing matrix via integrins α5β1 or αVβ3 can transfer stress tolerance to LPAR4-negative cells. Therefore, stress- or drug-induced LPAR4 enhances cell-autonomous production of a fibronectin-rich extracellular matrix, allowing cells to survive 'isolation stress' and compensate for the absence of stromal-derived factors by creating their own tumour-initiating niche.
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Affiliation(s)
- Chengsheng Wu
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - Taha Rakhshandehroo
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
- Department of Radiology, Dana-Farber Cancer Institute, Harvard University, Boston, MA, USA
| | - Hiromi I Wettersten
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - Alejandro Campos
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - Tami von Schalscha
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - Shashi Jain
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - Ziqi Yu
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - Jiali Tan
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - Evangeline Mose
- Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
| | - Betzaira G Childers
- Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
| | - Andrew M Lowy
- Division of Surgical Oncology, Department of Surgery, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
| | - Sara M Weis
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA
| | - David A Cheresh
- Department of Pathology, Moores Cancer Center, and Sanford Consortium for Regenerative Medicine at the University of California, San Diego, La Jolla, CA, USA.
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Yu D, Xin L, Qing X, Hao Z, Yong W, Jiangjiang Z, Yaqiu L. Key circRNAs from goat: discovery, integrated regulatory network and their putative roles in the differentiation of intramuscular adipocytes. BMC Genomics 2023; 24:51. [PMID: 36707755 PMCID: PMC9883971 DOI: 10.1186/s12864-023-09141-7] [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: 09/09/2022] [Accepted: 01/17/2023] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND The procession of preadipocytes differentiation into mature adipocytes involves multiple cellular and signal transduction pathways. Recently. a seirces of noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) were proved to play important roles in regulating differentiation of adipocytes. RESULT In this study, we aimed to identificate the potential circRNAs in the early and late stages of goat intramuscular adipocytes differentiation. Using bioinformatics methods to predict their biological functions and map the circRNA-miRNA interaction network. Over 104 million clean reads in goat intramuscular preadipocytes and adipocytes were mapped, of which16 circRNAs were differentially expressed (DE-circRNAs). Furthermore, we used real-time fluorescent quantitative PCR (qRT-PCR) technology to randomly detect the expression levels of 8 circRNAs among the DE-circRNAs, and our result verifies the accuracy of the RNA-seq data. From the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the DE-circRNAs, two circRNAs, circ_0005870 and circ_0000946, were found in Focal adhesion and PI3K-Akt signaling pathway. Then we draw the circRNA-miRNA interaction network and obtained the miRNAs that possibly interact with circ_0005870 and circ_0000946. Using TargetScan, miRTarBase and miR-TCDS online databases, we further obtained the mRNAs that may interact with the miRNAs, and generated the final circRNA-miRNA-mRNA interaction network. Combined with the following GO (Gene Ontology) and KEGG enrichment analysis, we obtained 5 key mRNAs related to adipocyte differentiation in our interaction network, which are FOXO3(forkhead box O3), PPP2CA (protein phosphatase 2 catalytic subunit alpha), EEIF4E (eukaryotic translation initiation factor 4), CDK6 (cyclin dependent kinase 6) and ACVR1 (activin A receptor type 1). CONCLUSIONS By using Illumina HiSeq and online databases, we generated the final circRNA-miRNA-mRNA interaction network that have valuable functions in adipocyte differentiation. Our work serves as a valuable genomic resource for in-depth exploration of the molecular mechanism of ncRNAs interaction network regulating adipocyte differentiation.
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Affiliation(s)
- Du Yu
- grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
| | - Li Xin
- grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
| | - Xu Qing
- grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
| | - Zhang Hao
- grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
| | - Wang Yong
- grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
| | - Zhu Jiangjiang
- grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China
| | - Lin Yaqiu
- grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China ,grid.412723.10000 0004 0604 889XCollege of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu, China
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20
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Oh KK, Gupta H, Min BH, Ganesan R, Sharma SP, Won SM, Jeong JJ, Lee SB, Cha MG, Kwon GH, Jeong MK, Hyun JY, Eom JA, Park HJ, Yoon SJ, Choi MR, Kim DJ, Suk KT. The identification of metabolites from gut microbiota in NAFLD via network pharmacology. Sci Rep 2023; 13:724. [PMID: 36639568 PMCID: PMC9839744 DOI: 10.1038/s41598-023-27885-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research.
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Affiliation(s)
- Ki-Kwang Oh
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Haripriya Gupta
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Byeong Hyun Min
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Raja Ganesan
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Satya Priya Sharma
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Sung Min Won
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Jin Ju Jeong
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Su Been Lee
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Min Gi Cha
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Goo Hyun Kwon
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Min Kyo Jeong
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Ji Ye Hyun
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Jung A Eom
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Hee Jin Park
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Sang Jun Yoon
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Mi Ran Choi
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Dong Joon Kim
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea
| | - Ki Tae Suk
- Center for Microbiome, Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, 24252, South Korea.
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21
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Yamazaki K, Miyauchi E, Kato T, Sato K, Suda W, Tsuzuno T, Yamada-Hara M, Sasaki N, Ohno H, Yamazaki K. Dysbiotic human oral microbiota alters systemic metabolism via modulation of gut microbiota in germ-free mice. J Oral Microbiol 2022; 14:2110194. [PMID: 35966937 PMCID: PMC9373767 DOI: 10.1080/20002297.2022.2110194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients. Aim We explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects. Methods The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Gut microbial communities, hepatic gene expression profiles, and serum metabolites were analyzed. Results The gut microbial composition was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of lipid and glucose metabolism-related genes. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with characteristic gut microbial taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice. Conclusion The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.
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Affiliation(s)
- Kyoko Yamazaki
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata Japan
| | - Eiji Miyauchi
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Kanagawa Japan
- Laboratory of Mucosal Ecosystem Design, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma Japan
| | - Tamotsu Kato
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Kanagawa Japan
- Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa Japan
| | - Keisuke Sato
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata Japan
| | - Wataru Suda
- Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Takahiro Tsuzuno
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata Japan
| | - Miki Yamada-Hara
- Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata Japan
| | - Nobuo Sasaki
- Laboratory of Mucosal Ecosystem Design, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma Japan
| | - Hiroshi Ohno
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Kanagawa Japan
- Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa Japan
- Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Kazuhisa Yamazaki
- Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Kanagawa Japan
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22
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Mukherjee AG, Wanjari UR, Gopalakrishnan AV, Katturajan R, Kannampuzha S, Murali R, Namachivayam A, Ganesan R, Renu K, Dey A, Vellingiri B, Prince SE. Exploring the Regulatory Role of ncRNA in NAFLD: A Particular Focus on PPARs. Cells 2022; 11:3959. [PMID: 36552725 PMCID: PMC9777112 DOI: 10.3390/cells11243959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/29/2022] [Accepted: 12/02/2022] [Indexed: 12/13/2022] Open
Abstract
Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD.
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Affiliation(s)
- Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Uddesh Ramesh Wanjari
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Ramkumar Katturajan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Sandra Kannampuzha
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Reshma Murali
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Arunraj Namachivayam
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Raja Ganesan
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Republic of Korea
| | - Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, Tamil Nadu, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata 700073, West Bengal, India
| | - Balachandar Vellingiri
- Stem Cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda 151401, Punjab, India
| | - Sabina Evan Prince
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
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23
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Wang J, Wang M, Shao J, Liu Z, Fu C, Chen G, Zhao K, Li H, Sun W, Jia X, Chen S, Lai S. Combined analysis of differentially expressed lncRNAs and miRNAs in liver tissues of high-fat fed rabbits by transcriptome sequencing. Front Genet 2022; 13:1000574. [PMID: 36276943 PMCID: PMC9585185 DOI: 10.3389/fgene.2022.1000574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
High-fat diet could lead to a series of metabolic diseases, including obesity, and its mechanism is not clear. In this study, the rabbit individuals were fed with high-fat diet, the liver tissues were collected, high-throughput sequencing technology was used to reveal the expression of lncRNA and miRNA difference, and the molecular regulation mechanism of lncRNA-miRNA. A total of 24,615 DE lncRNAs and 52 DE miRNAs were identified, including 15 novel discovered DE miRNAs (5 upregulated and 10 downregulated). Furthermore, five miRNAs and three mRNAs were verified by qRT-PCR, and the results showed that the expression of the DE miRNAs and DE lncRNAs in the two groups was consistent with our sequencing results. GO and KEGG analyzed 7,57,139 target genes respectively, enriching the pathways related to lipid metabolism, including mucin O-glycan biosynthesis pathway, insulin resistance and glucagon signaling pathway. Moreover, 65 targeting relationships were obtained. Among them, LOC103348122/miR-450a-5p, LOC103350359/miR-450a-3p and LOC103350429/miR-148a-5p were proposed the first time. Significantly, LOC103348122/miR-450a-5p and LOC103350429/miR-148a-5p were related to lipid metabolism in the liver. This study is of great significance to the CeRNA regulatory network related to lipid metabolism in the liver of rabbits, and provides a basis for understanding hepatic steatosis in rabbits.
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Affiliation(s)
- Jie Wang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Meigui Wang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Jiahao Shao
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Zheliang Liu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Chong Fu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Guanhe Chen
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Kaisen Zhao
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Hong Li
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Wenqiang Sun
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Xianbo Jia
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Shiyi Chen
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China
| | - Songjia Lai
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China
- *Correspondence: Songjia Lai,
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