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Qiu C, Chen Y, Xia H, Duan J, Zhang L, Zhang Y, Chen Z, Zhang L. Hsa_circ_0004662 Accelerates the Progression of Ulcerative Colitis via the microRNA-532/HMGB3 Signalling Axis. J Cell Mol Med 2025; 29:e70430. [PMID: 40099942 PMCID: PMC11916553 DOI: 10.1111/jcmm.70430] [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: 10/27/2024] [Revised: 12/18/2024] [Accepted: 02/04/2025] [Indexed: 03/20/2025] Open
Abstract
Increasing research has indicated that circular RNAs (circRNAs) are crucial for the development of ulcerative colitis (UC). Thus, we attempted to identify the role of hsa_circ_0004662 in UC progression. Hsa_circ_0004662 expression was determined via qRT-PCR. Lipopolysaccharide (LPS)-induced inflammation in normal colonic epithelial cells (ECs). The hsa_circ_0004662 content was then assessed in a mucosal inflammatory bowel disease (IBD) model. Cell proliferation was examined via CCK-8 and EdU uptake assays. Apoptotic rates were analysed via flow cytometry. The protein content was quantified via Western blotting. Enzyme-linked immunosorbent assay kits were used to detect IL-1β, TNF-α and IL-6, and dual-luciferase reporter (DLR) assays were used to identify interactions between miR-532 and circ_0004662 or HMGB3. An animal model of UC was also developed for confirmation. In this study, we identified the function of hsa_circ_0004662 in promoting UC progression. Hsa_circ_0004662 was upregulated in clinical UC tissues and LPS-induced colonic ECs, and its knockdown inhibited apoptosis, reduced inflammatory cytokine release and promoted cell proliferation in vitro. Mechanistically, hsa_circ_0004662 acted as a molecular sponge for miR-532, which targets HMGB3. The hsa_circ_0004662/miR-532/HMGB3 axis was further validated in a DSS-induced colitis mouse model, where hsa_circ_0004662 knockdown attenuated inflammation and tissue damage. These findings suggested that hsa_circ_0004662 contributes to UC progression through the miR-532/HMGB3 signalling pathway, offering potential targets for UC therapy.
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Affiliation(s)
- Chunhua Qiu
- Department of Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yun Chen
- Department of Geriatric Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Huan Xia
- Geriatrics Research Institute, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jun Duan
- Department of Geriatric Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Lu Zhang
- Department of Geriatric Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - You Zhang
- Department of Geriatric Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ziyang Chen
- Department of Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Li Zhang
- Department of Geriatric Gastroenterology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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Mukherjee S, Chopra A, Karmakar S, Bhat SG. Periodontitis increases the risk of gastrointestinal dysfunction: an update on the plausible pathogenic molecular mechanisms. Crit Rev Microbiol 2025; 51:187-217. [PMID: 38602474 DOI: 10.1080/1040841x.2024.2339260] [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: 11/04/2023] [Revised: 02/28/2024] [Accepted: 04/01/2024] [Indexed: 04/12/2024]
Abstract
Periodontitis is an immuno-inflammatory disease of the soft tissues surrounding the teeth. Periodontitis is linked to many communicable and non-communicable diseases such as diabetes, cardiovascular disease, rheumatoid arthritis, and cancers. The oral-systemic link between periodontal disease and systemic diseases is attributed to the spread of inflammation, microbial products and microbes to distant organ systems. Oral bacteria reach the gut via swallowed saliva, whereby they induce gut dysbiosis and gastrointestinal dysfunctions. Some periodontal pathogens like Porphyromonas. gingivalis, Klebsiella, Helicobacter. Pylori, Streptococcus, Veillonella, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus, Haemophilus, Aggregatibacter actinomycetomcommitans and Streptococcus mutans can withstand the unfavorable acidic, survive in the gut and result in gut dysbiosis. Gut dysbiosis increases gut inflammation, and induce dysplastic changes that lead to gut dysfunction. Various studies have linked oral bacteria, and oral-gut axis to various GIT disorders like inflammatory bowel disease, liver diseases, hepatocellular and pancreatic ductal carcinoma, ulcerative colitis, and Crohn's disease. Although the correlation between periodontitis and GIT disorders is well established, the intricate molecular mechanisms by which oral microflora induce these changes have not been discussed extensively. This review comprehensively discusses the intricate and unique molecular and immunological mechanisms by which periodontal pathogens can induce gut dysbiosis and dysfunction.
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Affiliation(s)
- Sayantan Mukherjee
- Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Aditi Chopra
- Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shaswata Karmakar
- Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Subraya Giliyar Bhat
- Department of Preventive Dental Sciences, Division of Periodontology, College of Dental Surgery, Iman Abdulrahman Bin Faizal University, Dammam, Saudi Arabia
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Kumar P, Kedia S, Ahuja V. Target potential of miRNAs in ulcerative colitis: what do we know? Expert Opin Ther Targets 2024; 28:829-841. [PMID: 39307951 DOI: 10.1080/14728222.2024.2408423] [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: 08/09/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 09/27/2024]
Abstract
INTRODUCTION The global rise in ulcerative colitis (UC) incidence highlights the urgent need for enhanced diagnostic and therapeutic strategies. Recent advances in genome-wide association studies (GWAS) have identified genetic loci associated with UC, providing insights into the disease's molecular mechanisms, including immune modulation, mucosal defense, and epithelial barrier function. Despite these findings, many GWAS signals are located in non-coding regions and are linked to low risk, suggesting that protein-coding genes alone do not fully explain UC's pathophysiology. Emerging research emphasizes the potential of microRNAs (miRNAs) as biomarkers and therapeutic targets due to their crucial role in UC. This review explores the current understanding of miRNAs in UC, including their mechanisms of action and their potential as both biomarkers and therapeutic targets. The present review provides the latest update on their potential as a biomarker and therapeutic target. AREAS COVERED This review synthesizes an extensive literature search on miRNAs in UC, focusing on their roles in the mucosal barrier, innate and adaptive immunity, and their potential applications as biomarkers and therapeutic modalities. EXPERT OPINION While miRNAs present promising opportunities as biomarkers and novel therapeutic agents in UC, challenges in validation, specificity, delivery, and clinical application need to be addressed through rigorous, large-scale studies.
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Affiliation(s)
- Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical sciences, New Delhi, India
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Moustafa HAM, Elsakka EGE, Abulsoud AI, Elshaer SS, Rashad AA, El-Dakroury WA, Sallam AAM, Rizk NI, Zaki MB, Gomaa RM, Elesawy AE, Mohammed OA, Abdel Mageed SS, Eleragi AMS, ElBoghdady JA, El-Fayoumi SH, Abdel-Reheim MA, Doghish AS. The miRNA Landscape in Crohn's disease: Implications for novel therapeutic approaches and interactions with Existing therapies. Exp Cell Res 2024; 442:114234. [PMID: 39233267 DOI: 10.1016/j.yexcr.2024.114234] [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: 07/16/2024] [Revised: 08/25/2024] [Accepted: 09/01/2024] [Indexed: 09/06/2024]
Abstract
MicroRNAs (miRNAs), which are non-coding RNAs consisting of 18-24 nucleotides, play a crucial role in the regulatory pathways of inflammatory diseases. Several recent investigations have examined the potential role of miRNAs in forming Crohn's disease (CD). It has been suggested that miRNAs serve as diagnostics for both fibrosis and inflammation in CD due to their involvement in the mechanisms of CD aggravation and fibrogenesis. More information on CD pathophysiology could be obtained by identifying the miRNAs concerned with CD and their target genes. These findings have prompted several in vitro and in vivo investigations into the putative function of miRNAs in CD treatment. Although there are still many unanswered questions, the growing body of evidence has brought miRNA-based therapy one step closer to clinical practice. This extensive narrative study offers a concise summary of the most current advancements in CD. We go over what is known about the diagnostic and therapeutic benefits of miRNA mimicry and inhibition so far, and we see what additional miRNA family targets could be useful for treating CD-related inflammation and fibrosis.
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Affiliation(s)
- Hebatallah Ahmed Mohamed Moustafa
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Shereen Saeid Elshaer
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Department of Biochemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo 11823, Egypt
| | - Ahmed A Rashad
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.
| | - Al-Aliaa M Sallam
- epartment of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Nehal I Rizk
- Biochemistry Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mohamed Bakr Zaki
- Biochemistry, Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt
| | - Rania M Gomaa
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr City, Cairo P.O. Box 11829, Egypt
| | - Ahmed E Elesawy
- epartment of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Osama A Mohammed
- Department of Pharmacology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Ali M S Eleragi
- Department of Microorganisms and Clinical Parasitology, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia
| | - Jasmine A ElBoghdady
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
| | - Shaimaa H El-Fayoumi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | | | - Ahmed S Doghish
- epartment of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt; Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
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Ramadan YN, Kamel AM, Medhat MA, Hetta HF. MicroRNA signatures in the pathogenesis and therapy of inflammatory bowel disease. Clin Exp Med 2024; 24:217. [PMID: 39259390 PMCID: PMC11390904 DOI: 10.1007/s10238-024-01476-z] [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: 06/04/2024] [Accepted: 08/20/2024] [Indexed: 09/13/2024]
Abstract
Inflammatory bowel disease (IBD) is a persistent inflammatory illness of the gastrointestinal tract (GIT) triggered by an inappropriate immune response to environmental stimuli in genetically predisposed persons. Unfortunately, IBD patients' quality of life is negatively impacted by the symptoms associated with the disease. The exact etiology of IBD pathogenesis is not fully understood, but the emerging research indicated that the microRNA (miRNA) plays an important role. miRNAs have been documented to possess a significant role in regulating pro- and anti-inflammatory pathways, in addition to their roles in several physiological processes, including cell growth, proliferation, and apoptosis. Variations in the miRNA profiles might be a helpful prognostic indicator and a valuable tool in the differential diagnosis of IBD. Most interestingly, these miRNAs have a promising therapeutic target in several pre-clinical animal studies and phase 2 clinical studies to alleviate inflammation and improve patient's quality of life. This comprehensive review discusses the current knowledge about the significant physiological role of different miRNAs in the health of the intestinal immune system and addresses the role of the most relevant differentially expressed miRNAs in IBD, identify their potential targets, and emphasize their diagnostic and therapeutic potential for future research.
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Affiliation(s)
- Yasmin N Ramadan
- Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut, 71515, Egypt.
| | - Ayat M Kamel
- Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut, 71515, Egypt
| | - Mohammed A Medhat
- Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt
| | - Helal F Hetta
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, 71491, Tabuk, Saudi Arabia
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Heydari R, Karimi P, Meyfour A. Long non-coding RNAs as pathophysiological regulators, therapeutic targets and novel extracellular vesicle biomarkers for the diagnosis of inflammatory bowel disease. Biomed Pharmacother 2024; 176:116868. [PMID: 38850647 DOI: 10.1016/j.biopha.2024.116868] [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: 04/07/2024] [Revised: 05/27/2024] [Accepted: 06/03/2024] [Indexed: 06/10/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal (GI) system that includes two groups, Crohn's disease (CD) and ulcerative colitis (UC). To cope with these two classes of IBD, the investigation of pathogenic mechanisms and the discovery of new diagnostic and therapeutic approaches are crucial. Long non-coding RNAs (lncRNAs) which are non-coding RNAs with a length of longer than 200 nucleotides have indicated significant association with the pathology of IBD and strong potential to be used as accurate biomarkers in diagnosing and predicting responses to the IBD treatment. In the current review, we aim to investigate the role of lncRNAs in the pathology and development of IBD. We first describe recent advances in research on dysregulated lncRNAs in the pathogenesis of IBD from the perspective of epithelial barrier function, intestinal immunity, mitochondrial function, and intestinal autophagy. Then, we highlight the possible translational role of lncRNAs as therapeutic targets, diagnostic biomarkers, and predictors of therapeutic response in colon tissues and plasma samples. Finally, we discuss the potential of extracellular vesicles and their lncRNA cargo in the pathophysiology, diagnosis, and treatment of IBD.
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Affiliation(s)
- Raheleh Heydari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Padideh Karimi
- CRTD/Center for Regenerative Therapies Dresden, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden 01307, Germany
| | - Anna Meyfour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Onisor D, Brusnic O, Banescu C, Carstea C, Sasaran M, Stoian M, Avram C, Boicean A, Boeriu A, Dobru D. miR-155 and miR-21 as Diagnostic and Therapeutic Biomarkers for Ulcerative Colitis: There Is Still a Long Way to Go. Biomedicines 2024; 12:1315. [PMID: 38927522 PMCID: PMC11201222 DOI: 10.3390/biomedicines12061315] [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: 05/12/2024] [Revised: 06/03/2024] [Accepted: 06/08/2024] [Indexed: 06/28/2024] Open
Abstract
(1) Elucidating the role of miRNAs (miRs) in ulcerative colitis may provide new insights into disease pathogenesis, diagnosis, treatment, and monitoring We aimed to investigate whether plasma levels of miR-21-5p and miR-155-5p may be used to differentiate between patients with organic disease such as ulcerative colitis (UC) and Clostridioides difficile infection (CDI), and patients with functional disease such as irritable bowel syndrome with diarrhea (IBS-D). (2) Serological samples were collected to quantify miR-155 and -21 expression, which was carried out through quantitative real-time polymerase chain reaction (qRT-PCR), from 84 patients: 34 with acute UC (group 1), 17 with CDI (group 2), and 33 with IBS-D (control group). (3) In this study, we found that the expression levels of miR-155-5p were almost the same for the two conditions and the control group (UC: 4.22 ± 1.61, CDI: 3.94 ± 1.62, IBS-D: 4.26 ± 1.26), with no significant differences either for ΔCt- or for ΔΔCt-derived parameters (p = 0.74 and p = 0.73, respectively). For miR-21, ΔCt levels presented significantly higher values among the ulcerative colitis group (p < 0.01), but the most important expression fold change was noticed in patients with CDI (UC:4.11 ± 8,46, CDI: 4.94 ± 9.68, IBS-D: 2.83 ± 5.41). (4) Circulating miR-155 and miR-21 were upregulated in UC, CDI, and IBS-D, but differentiation was not possible among them. But their involvement in the pathogenesis of the three diseases makes them suitable for improving the accuracy of diagnosis and facilitating the development of personalized treatment strategies.
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Affiliation(s)
- Danusia Onisor
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (D.O.); (A.B.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540072 Targu Mures, Romania
| | - Olga Brusnic
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (D.O.); (A.B.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540072 Targu Mures, Romania
| | - Claudia Banescu
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (C.B.); (C.C.)
| | - Claudia Carstea
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (C.B.); (C.C.)
| | - Maria Sasaran
- Department of Pediatrics III, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania;
| | - Mircea Stoian
- Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540139 Targu Mures, Romania;
| | - Calin Avram
- Department of Medical Informatics and Biostatistics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania
| | - Adrian Boicean
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania;
| | - Alina Boeriu
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (D.O.); (A.B.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540072 Targu Mures, Romania
| | - Daniela Dobru
- Department of Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gheorghe Marinescu Street No. 38, 540136 Targu Mures, Romania; (D.O.); (A.B.); (D.D.)
- Gastroenterology Department, Mureș County Clinical Hospital, 540072 Targu Mures, Romania
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Zhang M, Niu Z, Huang Q, Han L, Du J, Liang J, Cheng Y, Cao R, Yawalkar N, Zhang Z, Yan K. Identification of an exosomal miRNA-mRNA regulatory network contributing to methotrexate efficacy. Int Immunopharmacol 2024; 135:112280. [PMID: 38776848 DOI: 10.1016/j.intimp.2024.112280] [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: 08/12/2023] [Revised: 05/05/2024] [Accepted: 05/14/2024] [Indexed: 05/25/2024]
Abstract
OBJECTIVE Methotrexate (MTX) is an economic and effective medicine treatment for psoriasis. Extracellular vesicle (EV) miRNA biomarkers related to its efficiency have been identified in various diseases. Whether certain miRNA profiles are associated with psoriasis treatment is unknown. In order to determine specific miRNA biomarkers for MTX effectiveness prediction and the severity of psoriasis, our study looked at the variations in circulating EV miRNA profiles before and after MTX therapy. METHODS Plasma EV isolation and next-generation sequencing were performed to identify differentially expressed EV miRNAs between GRs (n = 14) and NRs (n = 6). Univariate and multiple linear regression analyses were performed to evaluate the correlation between PASI scores and miRNA expression levels. RESULTS 15 miRNAs out of a total profile of 443 miRNAs were substantially different between GRs and NRs at baseline, 4 of them (miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246) have the potential to distinguish between GRs and NRs [area under the curve (AUC) ≥ 0.70, all P < 0.05]. KEGG pathway analyses revealed differentially expressed miRNAs to potentially target immune-related pathways. SIRT1 was discovered to be a target of miR-199a-5p and involved in MAPK signaling pathway. MiR-191-5p and miR-21-5p expression levels have been discovered to positively correlate with PASI scores[P < 0.05]. CONCLUSION This pilot investigation found that miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246 might be prospective biomarkers to predict the efficacy of MTX, and that miR-191-5p and miR-21-5p were correlated with psoriasis severity. Five of them previously reported to be involved in MAPK signaling pathway, indicating a potential role of MTX in delaying the progression of psoriatic inflammation.
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Affiliation(s)
- Mengmeng Zhang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhenmin Niu
- Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai and Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
| | - Qiong Huang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ling Han
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Juan Du
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jun Liang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yanwen Cheng
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ruoshui Cao
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Nikhil Yawalkar
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Zhenghua Zhang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
| | - Kexiang Yan
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
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Vălean D, Zaharie R, Țaulean R, Usatiuc L, Zaharie F. Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review. Int J Mol Sci 2024; 25:2077. [PMID: 38396754 PMCID: PMC10889152 DOI: 10.3390/ijms25042077] [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: 01/16/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.
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Affiliation(s)
- Dan Vălean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roxana Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of Gastroenterology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roman Țaulean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Lia Usatiuc
- Department of Patophysiology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania;
| | - Florin Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
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Yan L, Gu C, Gao S, Wei B. Epigenetic regulation and therapeutic strategies in ulcerative colitis. Front Genet 2023; 14:1302886. [PMID: 38169708 PMCID: PMC10758477 DOI: 10.3389/fgene.2023.1302886] [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: 09/27/2023] [Accepted: 12/07/2023] [Indexed: 01/05/2024] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease, and is characterized by the diffuse inflammation and ulceration in the colon and rectum mucosa, even extending to the caecum. Epigenetic modifications, including DNA methylations, histone modifications and non-coding RNAs, are implicated in the differentiation, maturation, and functional modulation of multiple immune and non-immune cell types, and are influenced and altered in various chronic inflammatory diseases, including UC. Here we review the relevant studies revealing the differential epigenetic features in UC, and summarize the current knowledge about the immunopathogenesis of UC through epigenetic regulation and inflammatory signaling networks, regarding DNA methylation, histone modification, miRNAs and lncRNAs. We also discuss the epigenetic-associated therapeutic strategies for the alleviation and treatment of UC, which will provide insights to intervene in the immunopathological process of UC in view of epigenetic regulation.
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Affiliation(s)
- Liwei Yan
- The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, China
- Departments of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Chao Gu
- Departments of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Shanyu Gao
- Departments of Anorectal Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Benzheng Wei
- Center for Medical Artificial Intelligence, Shandong University of Traditional Chinese Medicine, Jinan, China
- Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China
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11
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Abdelazim SA, Shaker OG, Ali O, El-Tawil M, Senousy MA. Differential expression of serum miR-486 and miR-25 in ulcerative colitis and Crohn's disease: Correlations with disease activity, extent, and location. Pathol Res Pract 2023; 252:154910. [PMID: 37939427 DOI: 10.1016/j.prp.2023.154910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/23/2023] [Accepted: 10/24/2023] [Indexed: 11/10/2023]
Abstract
Novel reliable biomarkers of inflammatory bowel disease (IBD) are clinically imperative due to potential limitations of endoscopic techniques. MicroRNAs (miRNAs) have emerged as non-invasive biomarkers of IBD; however, the full disease-specific miRNAs signature for IBD subtypes remains elusive. We evaluated the diagnostic role of circulating miR-486 and miR-25 in IBD patients and their potential ability to discriminate IBD subtypes; ulcerative colitis (UC) and Crohn's disease (CD). Sixty UC patients, 60 CD patients, and 60 healthy controls were recruited. Serum miRNA expression was determined using RT-qPCR. Bioinformatics was employed for target gene and protein-protein interaction (PPI) network analyses. Serum miR-486 was upregulated in CD patients, but didn't change in UC patients compared to controls. Conversely, serum miR-25 was decreased in both CD and UC patients compared to controls. Only miR-486 was differentially expressed between UC and CD patients. Receiver-operating characteristic analysis revealed that serum miR-486 was superior in CD diagnosis (AUC=0.945) and significantly distinguished CD and UC patients, whereas miR-25 showed discriminative potential for both UC and CD from controls. In the multivariate logistic analysis only miR-486 was associated with the risk of CD diagnosis. Serum miR-486 was correlated with CD activity index and location of disease in CD patients, whereas miR-25 was correlated with the type/extent of UC. PPI network analysis revealed common target genes and signaling pathways for both miRNAs. Conclusively, serum miR-486 and miR-25 might serve as new biomarkers of IBD, with serum miR-486 could be employed in risk stratification of IBD subtypes and has the ground for clinical utility in CD diagnosis, whereas miR-25 has potential for UC and CD diagnosis.
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Affiliation(s)
- Samy A Abdelazim
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
| | - Olfat G Shaker
- Medical Biochemistry and Molecular Biology department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Omaima Ali
- Department of Biochemistry, Faculty of Pharmacy, Sinai University-Kantara Branch, Ismailia 41636, Egypt; General division for Biological Control and Research, Egyptian Drug Authority, Cairo 12618 Egypt
| | - Mai El-Tawil
- Neurology department, Kasr Al-Ainy Hospital, Cairo, Egypt
| | - Mahmoud A Senousy
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; Department of Biochemistry, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University, Cairo 11786, Egypt
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12
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Wang J, Yao M, Zou J, Ding W, Sun M, Zhuge Y, Gao F. pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:2797. [PMID: 37887947 PMCID: PMC10610125 DOI: 10.3390/nano13202797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 10/28/2023]
Abstract
Though the anti-miR-301a (anti-miR) is a promising treatment strategy for inflammatory bowel disease (IBD), the degradability and the poor targeting of the intestine are a familiar issue. This study aimed to develop a multifunctional oral nanoparticle delivery system loaded with anti-miR for improving the targeting ability and the therapeutic efficacy. The HA-CS/ES100/PLGA nanoparticles (HCeP NPs) were prepared using poly (lactic-co-glycolic acid) copolymer (PLGA), enteric material Eudragit®S100 (ES100), chitosan (CS), and hyaluronic acid (HA). The toxicity of nanoparticles was investigated via the Cell Counting Kit-8, and the cellular uptake and inflammatory factors of nanoparticles were further studied. Moreover, we documented the colon targeting and pharmacodynamic properties of nanoparticles. The nanoparticles with uniform particle size exhibited pH-sensitive release, favorable gene protection, and storage stability. Cytology experiments showed that anti-miR@HCeP NPs improved the cellular uptake through HA and reduced pro-inflammatory factors. Administering anti-miR@HCeP NPs orally to IBD mice markedly reduced their pro-inflammatory factors levels and disease activity indices. We also confirmed that anti-miR@HCeP NPs mostly accumulated in the colon site, and effectively repaired the intestinal barrier, as well as relieved intestinal inflammation. The above nanoparticle is a candidate of the treatment for IBD due to its anti-inflammatory properties.
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Affiliation(s)
- Junshan Wang
- Department of Gastroenterology, Chongming Branch of Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 202157, China
| | - Min Yao
- Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (M.Y.); (J.Z.); (W.D.); (M.S.)
| | - Jiafeng Zou
- Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (M.Y.); (J.Z.); (W.D.); (M.S.)
| | - Wenxing Ding
- Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (M.Y.); (J.Z.); (W.D.); (M.S.)
| | - Mingyue Sun
- Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (M.Y.); (J.Z.); (W.D.); (M.S.)
| | - Ying Zhuge
- Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
| | - Feng Gao
- Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; (M.Y.); (J.Z.); (W.D.); (M.S.)
- Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
- Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China
- Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
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D’Incà R, Sturniolo G. Biomarkers in IBD: What to Utilize for the Diagnosis? Diagnostics (Basel) 2023; 13:2931. [PMID: 37761298 PMCID: PMC10527829 DOI: 10.3390/diagnostics13182931] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/05/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process; the performance is better in Crohn's disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap, but the long half-life, the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.
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Affiliation(s)
- Renata D’Incà
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35124 Padua, Italy
| | - Giulia Sturniolo
- Department of Women’s and Children’s Health, University of Padua, 35128 Padova, Italy
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Brogaard L, Lyngby JG, Kristensen AT, Fredholm M, Bjørnvad CR, Salavati Schmitz S, Skancke E, Morris JS, Dupont N, Argyle D, Sánchez A, Spohr A, Graarup‐Hansen K, Nielsen LN, Cirera S. Association of serum and fecal microRNA profiles in cats with gastrointestinal cancer and chronic inflammatory enteropathy. J Vet Intern Med 2023; 37:1738-1749. [PMID: 37486176 PMCID: PMC10473000 DOI: 10.1111/jvim.16813] [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: 11/17/2022] [Accepted: 07/05/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Differentiation of gastrointestinal cancer (GIC) from chronic inflammatory enteropathies (CIE) in cats can be challenging and often requires extensive diagnostic testing. MicroRNAs (miRNAs) have promise as non-invasive biomarkers in serum and feces for diagnosis of GIC. HYPOTHESIS/OBJECTIVES Cats with GIC will have serum and fecal miRNA profiles that differ significantly from healthy cats and cats with CIE. Identify serum and fecal miRNAs with diagnostic potential for differentiation between cats with GIC and CIE as compared to healthy cats. ANIMALS Ten healthy cats, 9 cats with CIE, and 10 cats with GIC; all client-owned. METHODS Cats were recruited for an international multicenter observational prospective case-control study. Serum and feces were screened using small RNA sequencing for miRNAs that differed in abundance between cats with GIC and CIE, and healthy cats. Diagnostic biomarker potential of relevant miRNAs from small RNA sequencing and the literature was confirmed using reverse transcription quantitative real-time PCR (RT-qPCR). RESULTS Serum miR-223-3p was found to distinguish between cats with GIC and CIE with an area under the curve (AUC) of 0.9 (95% confidence interval [CI], 0.760-1.0), sensitivity of 90% (95% CI, 59.6-99.5%), and specificity of 77.8% (95% CI, 45.3-96.1%). Serum miR-223-3p likewise showed promise in differentiating a subgroup of cats with small cell lymphoma (SCL) from those with CIE. No fecal miRNAs could distinguish between cats with GIC and CIE. CONCLUSION AND CLINICAL IMPORTANCE Serum miR-223-3p potentially may serve as a noninvasive diagnostic biomarker of GIC in cats, in addition to providing a much needed tool for the differentiation of CIE and SCL.
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Affiliation(s)
- Louise Brogaard
- Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
- Present address:
Department of Biotechnology and BiomedicineTechnical University of DenmarkLyngbyDenmark
| | - Janne G. Lyngby
- Department of Veterinary Clinical SciencesUniversity of CopenhagenFrederiksbergDenmark
| | | | - Merete Fredholm
- Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Charlotte R. Bjørnvad
- Department of Veterinary Clinical SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Silke Salavati Schmitz
- Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, The Roslin Institute, College of Medicine and Veterinary Medicine, University of EdinburghMidlothianUK
| | - Ellen Skancke
- Department of Companion Animal Clinical SciencesNorwegian University of the Life SciencesOsloNorway
| | - Joanna S. Morris
- College of Medical, Veterinary, and Life Sciences, School of Veterinary Medicine, University of GlasgowGlasgowUK
| | - Nana Dupont
- Department of Veterinary Clinical SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - David Argyle
- Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, The Roslin Institute, College of Medicine and Veterinary Medicine, University of EdinburghMidlothianUK
| | - Armand Sánchez
- Department of Animal Medicine and Surgery, School of Veterinary SciencesUniversitat Autònoma de Barcelona, Cerdanyola del VallèsBarcelonaSpain
- Centre for Research in Agricultural Genomics, The Spanish National Research Council (CSIC)Institute of Agrifood Research and Technology (IRTA), Autonomous University of Barcelona (UAB), and University of Barcelona (UB)BarcelonaSpain
| | | | | | - Lise N. Nielsen
- Department of Veterinary Clinical SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Susanna Cirera
- Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
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15
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Wu Z, Yan Y, Li W, Li Y, Yang H. Expression Profile of miR-199a and Its Role in the Regulation of Intestinal Inflammation. Animals (Basel) 2023; 13:1979. [PMID: 37370489 DOI: 10.3390/ani13121979] [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: 05/08/2023] [Revised: 05/28/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
Early weaning stress impairs intestinal health in piglets. miRNAs are crucial for maintaining host homeostasis, while their implication for animal health remains unclear. To identify weaning-associated miRNAs, piglets were sampled at day 0, 1, 3, 7 and 14 after weaning. The data indicated that the highest levels of miR-199a-5p in jejunal villus upper cells were observed on day 14 after weaning, while the lowest levels in crypt cells were noted on day 7 and 14. In contrast, miR-199a-3p was down-regulated in both of these two cells on day 7 after weaning compared with day 0. Both miR-199a-5p and -3p were differently expressed along the villus-crypt axis. To further clarify the function of miR-199a, mice deficient in miR-199a were exposed to dextran sulfate sodium (DSS) to induce colitis. Results revealed that silencing of miR-199a enhanced sensitivity to DSS-induced colitis. Moreover, the increased morbidity and mortality were correlated with enhanced inflammatory cell infiltration, elevated pro-inflammatory cytokine expression, impaired barrier function, and a concomitant increase in permeability-related parameters. Bioinformatic analysis further demonstrated that lipid metabolism-related pathways were significantly enriched and Ndrg1 was verified as a target of miR-199a-3p. These findings indicate that miR-199a may be important for animal health management.
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Affiliation(s)
- Zijuan Wu
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan Normal University, No. 36 Lushan Road, Changsha 410081, China
| | - Yanyun Yan
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan Normal University, No. 36 Lushan Road, Changsha 410081, China
| | - Wenli Li
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan Normal University, No. 36 Lushan Road, Changsha 410081, China
| | - Yali Li
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan Normal University, No. 36 Lushan Road, Changsha 410081, China
| | - Huansheng Yang
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan Normal University, No. 36 Lushan Road, Changsha 410081, China
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16
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Silina MV, Dzhalilova DS, Makarova OV. Role of MicroRNAs in Regulation of Cellular Response to Hypoxia. BIOCHEMISTRY. BIOKHIMIIA 2023; 88:741-757. [PMID: 37748871 DOI: 10.1134/s0006297923060032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/13/2023] [Accepted: 04/13/2023] [Indexed: 09/27/2023]
Abstract
Hypoxia causes changes in transcription of the genes that contribute to adaptation of the cells to low levels of oxygen. The main mechanism regulating cellular response to hypoxia is activation of hypoxia-inducible transcription factors (HIF), which include several isoforms and control expression of more than a thousand genes. HIF activity is regulated at various levels, including by small non-coding RNA molecules called microRNAs (miRNAs). miRNAs regulate cellular response to hypoxia by influencing activation of HIF, its degradation, and translation of HIF-dependent proteins. At the same time, HIFs also affect miRNAs biogenesis. Data on the relationship of a particular HIF isoform with miRNAs are contradictory, since studies have been performed using different cell lines, various types of experimental animals and clinical material, as well as at different oxygen concentrations and durations of hypoxic exposure. In addition, HIF expression may be affected by the initial resistance of organisms to lack of oxygen, which has not been taken into account in the studies. This review analyzes the data on the effect of hypoxia on biogenesis and functioning of miRNAs, as well as on the effect of miRNAs on mRNAs of the genes involved in adaptation to oxygen deficiency. Understanding the mechanisms of relationship between HIF, hypoxia, and miRNA is necessary to develop new approaches to personalized therapy for diseases accompanied by oxygen deficiency.
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Affiliation(s)
- Maria V Silina
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, 117418, Russia.
| | - Dzhuliia Sh Dzhalilova
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, 117418, Russia
| | - Olga V Makarova
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, Moscow, 117418, Russia
- Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234, Russia
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17
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Alfaifi J, Germain A, Heba AC, Arnone D, Gailly L, Ndiaye NC, Viennois E, Caron B, Peyrin-Biroulet L, Dreumont N. Deep Dive Into MicroRNAs in Inflammatory Bowel Disease. Inflamm Bowel Dis 2023; 29:986-999. [PMID: 36545755 DOI: 10.1093/ibd/izac250] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Indexed: 06/02/2023]
Abstract
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is thought to develop in genetically predisposed individuals as a consequence of complex interactions between dysregulated inflammatory stimuli, immunological responses, and environmental factors. The pathogenesis of IBD has yet to be fully understood. The global increase in the incidence of IBD suggests a gap in the current understanding of the disease. The development of a new diagnostic tool for inflammatory bowel disease that is both less invasive and more cost-effective would allow for better management of this condition. MicroRNAs (miRNAs) are a class of noncoding RNAs with important roles as posttranscriptional regulators of gene expression, which has led to new insights into understanding IBD. Using techniques such as microarrays and real-time polymerase chain reactions, researchers have investigated the patterns in which patients with Crohn's disease and ulcerative colitis show alterations in the expression of miRNA in tissue, blood, and feces. These miRNAs are found to be differentially expressed in IBD and implicated in its pathogenesis through alterations in autophagy, intestinal barrier, and immune homeostasis. In this review, we discuss the miRNA expression profiles associated with IBD in tissue, peripheral blood, and feces and provide an overview of the miRNA mechanisms involved in IBD.
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Affiliation(s)
- Jaber Alfaifi
- Department of Hepatobiliary, Colorectal, and Digestive Surgery, Nancy University Hospital, University of Lorraine, Nancy, France
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Adeline Germain
- Department of Hepatobiliary, Colorectal, and Digestive Surgery, Nancy University Hospital, University of Lorraine, Nancy, France
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Anne-Charlotte Heba
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Djésia Arnone
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Laura Gailly
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Ndeye Coumba Ndiaye
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
| | - Emilie Viennois
- INSERM U1149, Center of Research on Inflammation, Université de Paris, Paris, France
| | - Bénédicte Caron
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
- Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Nancy, France
| | - Laurent Peyrin-Biroulet
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
- Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Nancy, France
| | - Natacha Dreumont
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), INSERM, University of Lorraine, Nancy, France
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Elahimanesh M, Najafi M. Cross talk between bacterial and human gene networks enriched using ncRNAs in IBD disease. Sci Rep 2023; 13:7704. [PMID: 37169818 PMCID: PMC10175251 DOI: 10.1038/s41598-023-34780-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 05/08/2023] [Indexed: 05/13/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a long-term inflammatory immune-mediated gut illness with several extra-intestinal complications. The aims of this study were to identify a novel network-based meta-analysis approach on the basis of the combinations of the differentially expressed genes (DEGs) from microarray data, to enrich the functional modules from human protein-protein interaction (PPI) and gene ontology (GO) data, and to profile the ncRNAs on the genes involved in IBD. The gene expression profiles of GSE126124, GSE87473, GSE75214, and GSE95095 are obtained from the Gene Expression Omnibus (GEO) database based on the study criteria between 2017 and 2022. The DEGs were screened by the R software. DEGs were then used to examine gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The ncRNAs including the miRNAs and ceRNAs were predicted on the PPIs visualized using Cytoscape. Enrichment analysis of genes with differential expression (n = 342) using KEGG and GO showed that the signaling pathways related with staphylococcus aureus and pertussis bacterial infections may stimulate the immune system and exacerbate IBD via the interaction with human proteins including Fibrinogen gamma chain (FGG), Keratin 10 (KRT10), and Toll like receptor 4 (TLR4). By building a ceRNA network, lncRNA XIST and NEAT1 were determined by affecting common miRNAs, hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-6763-5p, hsa-miR-4436a, and hsa-miR-520a-5p. Additionally, the chromosome regions including NM_001039703 and NM_006267, which produce the most potent circRNAs play a significant role in the ceRNA network of IBD. Also, we predicted the siRNAs that would be most effective against the bacterial genes in staphylococcus aureus and pertussis infections. These findings suggested that three genes (FGG, KRT10, and TLR4), six miRNAs (hsa-miR-6875-5p, hsa-miR-1908-5p, hsa-miR-186-5p, hsa-miR-4436a, hsa-miR-520a-5p, and hsa-miR-6763-5p), two lncRNAs (XIST and NEAT1), and chromosomal regions including NM_001039703 and NM_006267 with the production of the most effective circRNAs are involved in the ncRNA-associated ceRNA network of IBD. These ncRNA profiles are related to the described gene functions and may play therapeutic targets in controlling inflammatory bowel disease.
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Affiliation(s)
- Mohammad Elahimanesh
- Clinical Biochemistry Department, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Najafi
- Clinical Biochemistry Department, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.
- Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran.
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19
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Zhou F, Chen L, Xu S, Si C, Li N, Dong H, Zheng P, Wang W. Upregulation of miR-151-5p promotes the apoptosis of intestinal epithelial cells by targeting brain-derived neurotrophic factor in ulcerative colitis mice. Cell Cycle 2022; 21:2615-2626. [PMID: 35938703 PMCID: PMC9704397 DOI: 10.1080/15384101.2022.2105905] [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: 11/28/2021] [Revised: 06/14/2022] [Accepted: 07/19/2022] [Indexed: 01/09/2023] Open
Abstract
Ulcerative colitis (UC) is the most prevalent form of chronic inflammatory bowel disease, the etiology of which is poorly understood. This study investigated the role of miR-151-5p on UC and explored the role of brain-derived neurotrophic factor (BDNF) in a UC mouse model and cell model. A UC mouse model was engineered by dextran sulfate sodium (DSS) induction. Primary mouse intestinal epithelial cells (IECs) were isolated. Colitis mice were intraperitoneally injected with miR-151-5p antagomir and antagomir negative control, and weight loss, disease activity index, and colon length of mice were measured. Colon tissues of mice were histologically analyzed. A UC cell model was constructed by treating MODE-K cells with DSS. miR-151-5p expression in the cell model was modulated by transfection. The exogenous BDNF effect on the UC cell model and intestinal cell apoptosis, viability and proliferation was detected by flow cytometry, CCK-8 and EdU experiment. The expression of miR-151-5p and apoptosis-related proteins was assessed through q-PCR and western blotting. miR-151-5p was upregulated in the colon tissues and primary IECs of colitis mice. miR-151-5p directly inhibited the expression of BNDF. miR-151-5p upregulation promoted apoptosis in UC MODE-K cells. miR-151-5p upregulation repressed the viability of UC MODE-K cells. Exogenous BNDF treatment reversed the effect of miR-151-5p on UC MODE-K cells. miR-151-5p knockdown improved UC symptoms in mice, including alleviating weight loss, reducing disease activity index and improving colon length and damaged colon tissues. miR-151-5p contributed to intestinal epithelial cells apoptosis in colitis mice via inhibiting BNDF expression.
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Affiliation(s)
- Feng Zhou
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
| | - Lipeng Chen
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
| | - Shan Xu
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
| | - Caijuan Si
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
| | - Nan Li
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
| | - Hui Dong
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
| | - Peifen Zheng
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
| | - Weifeng Wang
- Department of gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang, P.R. China
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20
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Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases. Clin Rev Allergy Immunol 2022; 63:447-471. [DOI: 10.1007/s12016-022-08956-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/07/2022] [Indexed: 11/11/2022]
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Rosso AD, Aguilera P, Quesada S, Mascardi F, Mascuka SN, Cimolai MC, Cerezo J, Spiazzi R, Conlon C, Milano C, Iraola GM, Penas-Steinhardt A, Belforte FS. Comprehensive Phenotyping in Inflammatory Bowel Disease: Search for Biomarker Algorithms in the Transkingdom Interactions Context. Microorganisms 2022; 10:2190. [PMID: 36363782 PMCID: PMC9698371 DOI: 10.3390/microorganisms10112190] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/27/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022] Open
Abstract
Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn's disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context.
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Affiliation(s)
- Ayelén D. Rosso
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto de Ecología y Desarrollo Sustentable (INEDES-CONICET-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
| | - Pablo Aguilera
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
| | - Sofía Quesada
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
| | - Florencia Mascardi
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), CONICET, Instituto Universitario del Hospital Italiano (IUHI), Hospital Italiano de Buenos Aires (HIBA), Ciudad Autónoma de Buenos Aires C1199, Argentina
| | - Sebastian N. Mascuka
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
| | - María C. Cimolai
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
| | - Jimena Cerezo
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Renata Spiazzi
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Carolina Conlon
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Claudia Milano
- Servicio de Gastroenterología, Hospital Nacional Prof. Alejandro Posadas, Ciudad Autónoma de Buenos Aires 1704, Argentina
| | - Gregorio M. Iraola
- Laboratorio de Genómica Microbiana, Institut Pasteur Montevideo, Montevideo 11400, Uruguay
- Centro de Biología Integrativa, Universidad Mayor, Santiago 7510041, Chile
- Wellcome Sanger Institute, Wellcome Genome Campus, Cambridgeshire CB10 1SA, UK
| | - Alberto Penas-Steinhardt
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto Universitario de Ciencias de la Salud, Fundación H.A. Barceló, Ciudad Autónoma de Buenos Aires 1127, Argentina
| | - Fiorella S. Belforte
- Laboratorio de Genómica Computacional (GeC-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Programa del Estudio de Comunicación y Señalización Interreino (PECSI-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires C1425FQB, Argentina
- Instituto de Ecología y Desarrollo Sustentable (INEDES-CONICET-UNLu), Departamento de Ciencias Básicas, Universidad Nacional de Luján, Luján 6700, Argentina
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22
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Xu S, Chen S, Zhang M, An W, Li J, Sun Z, Xu Y. Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on Competitive Endogenous RNAs in Ulcerative Colitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:4572181. [PMID: 36310619 PMCID: PMC9616663 DOI: 10.1155/2022/4572181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 10/08/2022] [Indexed: 11/24/2022]
Abstract
Ulcerative colitis (UC) is a common autoimmune disease worldwide. Circular RNA (circRNA) is a type of noncoding ribonucleic acids (ncRNAs). In addition to their roles in numerous biological processes, circRNAs are also linked to a vast range of diseases including UC. Although previous studies have examined many circRNAs, the physiological and pathological roles of the circRNA-associated competing endogenous RNA (ceRNA) network in UC remain unclear. Thus, we constructed a circRNA-miRNA-mRNA network based on the ceRNA hypothesis by analyzing data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) database. Genes with higher degree values than others in the ceRNA network were selected as central nodes when constructing the corresponding core subnetworks. To fully understand the biological function of the ceRNA network, we entered all differentially expressed mRNAs (DEmRNAs) from the ceRNA network into the Database for Annotation and Integrated Discovery (DAVID), which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We further entered DEmRNAs into the STRING database for protein-protein interaction (PPI) network analysis. The results elucidated that the ceRNA network comprised 403 circRNA nodes, 5 miRNA nodes, 138 mRNA nodes, and 559 edges. Three core ceRNA subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p, and hsa-miR-142-3p were reconstructed in this study. GO and KEGG enrichment analyses identified 167 enriched GO categories and 14 enriched KEGG pathway terms. The core PPI network was composed of 15 core targets, of which CD44, HIF1A, and MMP2 were the most significant. In summary, 3 hub miRNAs (hsa-miR-342-3p, hsa-miR-199a-5p, hsa-miR-142-3p) and 3 hub genes (CD44, HIF1A, and MMP2) might play an important role in the development of UC. These hub nodes, first proposed here, might also be used as potential diagnostic markers and therapeutic targets.
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Affiliation(s)
- Sai Xu
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Shouqiang Chen
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Menghe Zhang
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Wenrong An
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Jie Li
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Zhenhai Sun
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
| | - Yunsheng Xu
- Shandong University of Traditional Chinese Medicine, Jinan, China
- Second Affiliated Hospital of Shandong University of TCM, Jinan, China
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23
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Chen H, Li P, Chen J, Wang Y, Yu Q, Wu Y, Chen Y, Cai J. Peripheral blood mononuclear cell microRNAs are novel biomarkers for diagnosing and monitoring Crohn's disease. FASEB J 2022; 36:e22549. [PMID: 36165177 DOI: 10.1096/fj.202200452r] [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: 03/24/2022] [Revised: 08/07/2022] [Accepted: 09/02/2022] [Indexed: 11/11/2022]
Abstract
Crohn's disease is a recurrent, progressive, immune-mediated inflammatory disease and merely manifests non-specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT-PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR-582-5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606-0.796, p < .001). While PBMC miR-96-5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p < .001) and endoscopic activity (ρ = 0.512, p = .015). Furthermore, PBMC miR-96-5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609-0.844, p = .001) than C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR-582-5p may be further utilized as a diagnostic biomarker, while miR-96-5p may be a novel and valuable biomarker in monitoring disease activity.
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Affiliation(s)
- Hanwen Chen
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Peiwei Li
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Jiamin Chen
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Yufang Wang
- Department of Gastroenterology, The Third People's Hospital of Hangzhou, Hangzhou, P. R. China
| | - Qiao Yu
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Yihua Wu
- Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, P. R. China
| | - Yan Chen
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Jianting Cai
- Center of Inflammatory Bowel Disease, Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
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24
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Lyngby JG, Gòdia M, Brogaard L, Kristensen AT, Fredholm M, Skancke E, Morris J, Dupont N, Salavati Schmitz S, Argyle D, Sánchez A, Bjørnvad CR, Cirera S, Nielsen LN. Association of fecal and serum microRNA profiles with gastrointestinal cancer and chronic inflammatory enteropathy in dogs. Vet Med (Auckl) 2022; 36:1989-2001. [PMID: 36120988 DOI: 10.1111/jvim.16530] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 08/18/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Reliable biomarkers to differentiate gastrointestinal cancer (GIC) from chronic inflammatory enteropathy (CIE) in dogs are needed. Fecal and serum microRNAs (miRNAs) have been proposed as diagnostic and prognostic markers of GI disease in humans and dogs. HYPOTHESIS/OBJECTIVES Dogs with GIC have fecal and serum miRNA profiles that differ from those of dogs with CIE. AIMS (a) identify miRNAs that differentiate GIC from CIE, (b) use high-throughput reverse transcription quantitative real-time PCR (RT-qPCR) to establish fecal and serum miRNA panels to distinguish GIC from CIE in dogs. ANIMALS Twenty-four dogs with GIC, 10 dogs with CIE, and 10 healthy dogs, all client-owned. METHODS An international multicenter observational prospective case-control study. Small RNA sequencing was used to identify fecal and serum miRNAs, and RT-qPCR was used to establish fecal and serum miRNA panels with the potential to distinguish GIC from CIE. RESULTS The best diagnostic performance for distinguishing GIC from CIE was fecal miR-451 (AUC: 0.955, sensitivity: 86.4%, specificity: 100%), miR-223 (AUC: 0.918, sensitivity: 90.9%, specificity: 80%), and miR-27a (AUC: 0.868, sensitivity: 81.8%, specificity: 90%) and serum miR-20b (AUC: 0.905, sensitivity: 90.5%, specificity: 90%), miR-148a-3p (AUC: 0.924, sensitivity: 85.7%, specificity: 90%), and miR-652 (AUC: 0.943, sensitivity: 90.5%, specificity: 90%). Slightly improved diagnostic performance was achieved when combining fecal miR-451 and miR-223 (AUC: 0.973, sensitivity: 95.5%, specificity: 90%). CONCLUSIONS AND CLINICAL IMPORTANCE When used as part of a diagnostic RT-qPCR panel, the abovementioned miRNAs have the potential to function as noninvasive biomarkers for the differentiation of GIC and CIE in dogs.
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Affiliation(s)
- Janne G Lyngby
- Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Marta Gòdia
- Department of Animal Medicine and Surgery, School of Veterinary Sciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Catalonia, Spain.,Centre for Research in Agricultural Genomics, The Spanish National Research Council (CSIC), Institute of Agrifood Research and Technology (IRTA), Autonomous University of Barcelona (UAB), and University of Barcelona (UB), Cerdanyola del Vallès, Catalonia, Spain.,Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Louise Brogaard
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Annemarie T Kristensen
- Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Merete Fredholm
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ellen Skancke
- Department of Companion Animal Clinical Sciences, Norwegian University of the Life Sciences, Oslo, Norway
| | - Joanna Morris
- College of Medical, Veterinary and Life Sciences, School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom
| | - Nana Dupont
- Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Silke Salavati Schmitz
- Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, The Roslin Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Easter Bush, Midlothian, United Kingdom
| | - David Argyle
- Hospital for Small Animals, Royal (Dick) School of Veterinary Studies, The Roslin Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Easter Bush, Midlothian, United Kingdom
| | - Armand Sánchez
- Department of Animal Medicine and Surgery, School of Veterinary Sciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Catalonia, Spain.,Centre for Research in Agricultural Genomics, The Spanish National Research Council (CSIC), Institute of Agrifood Research and Technology (IRTA), Autonomous University of Barcelona (UAB), and University of Barcelona (UB), Cerdanyola del Vallès, Catalonia, Spain
| | - Charlotte R Bjørnvad
- Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Susanna Cirera
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Lise N Nielsen
- Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
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25
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MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23147991. [PMID: 35887337 PMCID: PMC9318064 DOI: 10.3390/ijms23147991] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/13/2022] [Accepted: 07/18/2022] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD). These are autoimmune diseases of the gastrointestinal tract with a chronic relapsing and remitting course. Due to complex interactions between multiple factors in the etiology of IBD, the discovery of new predictors of disease course and response to therapy, and the development of effective therapies is a significant challenge. The dysregulation of microRNAs (miRNAs), a class of conserved endogenous, small non-coding RNA molecules with a length of 18–25 nucleotides, that regulate gene expression by an RNA interference process, is implicated in the complex pathogenetic context of IBD. Both tissue-derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of disease severity of IBD. In this review, we summarize the expressed miRNA profile in blood, mucosal tissue, and stool and highlight the role of miRNAs as biomarkers with potential diagnostic and therapeutic applications in ulcerative colitis and Crohn’s disease. Moreover, we discuss the new perspectives in developing a new screening model for the detection of colorectal cancer (CRC) based on fecal miRNAs.
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26
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The Current Status of Molecular Biomarkers for Inflammatory Bowel Disease. Biomedicines 2022; 10:biomedicines10071492. [PMID: 35884797 PMCID: PMC9312796 DOI: 10.3390/biomedicines10071492] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/20/2022] [Accepted: 06/21/2022] [Indexed: 12/12/2022] Open
Abstract
Diagnosis and prognosis of inflammatory bowel disease (IBD)-a chronic inflammation that affects the gastrointestinal tract of patients-are challenging, as most clinical symptoms are not specific to IBD, and are often seen in other inflammatory diseases, such as intestinal infections, drug-induced colitis, and monogenic diseases. To date, there is no gold-standard test for monitoring IBD. Endoscopy and imaging are essential diagnostic tools that provide information about the disease's state, location, and severity. However, the invasive nature and high cost of endoscopy make it unsuitable for frequent monitoring of disease activity in IBD patients, and even when it is possible to replace endoscopy with imaging, high cost remains a concern. Laboratory testing of blood or feces has the advantage of being non-invasive, rapid, cost-effective, and standardizable. Although the specificity and accuracy of laboratory testing alone need to be improved, it is increasingly used to monitor disease activity or to diagnose suspected IBD cases in combination with endoscopy and/or imaging. The literature survey indicates a dearth of summarization of biomarkers for IBD testing. This review introduces currently available non-invasive biomarkers of clinical importance in laboratory testing for IBD, and discusses the trends and challenges in the IBD biomarker studies.
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27
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Yarani R, Shojaeian A, Palasca O, Doncheva NT, Jensen LJ, Gorodkin J, Pociot F. Differentially Expressed miRNAs in Ulcerative Colitis and Crohn’s Disease. Front Immunol 2022; 13:865777. [PMID: 35734163 PMCID: PMC9208551 DOI: 10.3389/fimmu.2022.865777] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 04/13/2022] [Indexed: 12/14/2022] Open
Abstract
Differential microRNA (miRNA or miR) regulation is linked to the development and progress of many diseases, including inflammatory bowel disease (IBD). It is well-established that miRNAs are involved in the differentiation, maturation, and functional control of immune cells. miRNAs modulate inflammatory cascades and affect the extracellular matrix, tight junctions, cellular hemostasis, and microbiota. This review summarizes current knowledge of differentially expressed miRNAs in mucosal tissues and peripheral blood of patients with ulcerative colitis and Crohn’s disease. We combined comprehensive literature curation with computational meta-analysis of publicly available high-throughput datasets to obtain a consensus set of miRNAs consistently differentially expressed in mucosal tissues. We further describe the role of the most relevant differentially expressed miRNAs in IBD, extract their potential targets involved in IBD, and highlight their diagnostic and therapeutic potential for future investigations.
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Affiliation(s)
- Reza Yarani
- Translational Type 1 Diabetes Research, Department of Clinical Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States
- *Correspondence: Reza Yarani, ; Flemming Pociot,
| | - Ali Shojaeian
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Oana Palasca
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nadezhda T. Doncheva
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Lars Juhl Jensen
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
| | - Jan Gorodkin
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Pociot
- Translational Type 1 Diabetes Research, Department of Clinical Research, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Center for Non-Coding RNA in Technology and Health, University of Copenhagen, Copenhagen, Denmark
- Copenhagen Diabetes Research Center, Department of Pediatrics, Herlev University Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- *Correspondence: Reza Yarani, ; Flemming Pociot,
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28
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Circulating Exosomal miR-144-3p from Crohn’s Disease Patients Inhibits Human Umbilical Vein Endothelial Cell Function by Targeting FN1. DISEASE MARKERS 2022; 2022:8219557. [PMID: 35692876 PMCID: PMC9184168 DOI: 10.1155/2022/8219557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 04/20/2022] [Indexed: 11/20/2022]
Abstract
Background Crohn's disease (CD) is a chronic nonspecific inflammatory disease with unknown pathogenesis and vascular changes associated with the progression of CD. Many studies have shown that miRNAs participate in the development of CD. However, the effect of miRNAs in circulating exosomes on vascular endothelial cells in CD has not been investigated. Our study is aimed at identifying the differential miRNAs in circulating exosomes in CD and exploring their potential roles in human umbilical vein endothelial cells (HUVECs). Methods In our study, exosomes were extracted from circulating blood to identify differential miRNAs. After in vitro transfection of HUVECs with miR-144-3p mimics and inhibitors and the corresponding controls, cell counting kit-8, wound healing, Transwell migration, and tube formation assays were performed to study the viability, migration, and angiogenesis of HUVECs. Furthermore, bioinformatics analysis was used to predict miRNA targets. Western blotting was used to determine protein expression. In addition, exogenous supplementation with the fibronectin 1 (FN1) protein rescued the effects of miR-144-3p on changes in cell function in vitro. Results miR-144-3p was significantly increased in circulating exosomes of patients with CD compared with those in the control group. The promotion or inhibition of miR-144-3p correspondingly abolished or accelerated cell viability, migration, and angiogenesis. FN1 is a significant target of miR-144-3p, and exogenous FN1 administration improved the function of HUVECs in vitro. Conclusions Circulating exosomal miR-144-3p from patients with active CD contributes to vascular endothelial dysfunction by affecting the gene expression of FN1. These findings suggested that circulating exosomal miR-144-3p could be a potential biological marker for CD.
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29
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Xiao X, Mao X, Chen D, Yu B, He J, Yan H, Wang J. miRNAs Can Affect Intestinal Epithelial Barrier in Inflammatory Bowel Disease. Front Immunol 2022; 13:868229. [PMID: 35493445 PMCID: PMC9043318 DOI: 10.3389/fimmu.2022.868229] [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: 02/02/2022] [Accepted: 03/18/2022] [Indexed: 11/17/2022] Open
Abstract
The most obvious pathological characterization of inflammatory bowel disease (IBD) is intestinal epithelium erosion and severe inflammation invasion. Micro-ribonucleic acids (miRNA or microRNA), single-stranded noncoding RNAs of ~22 nucleotides, have been considered as the potential therapeutic targets in the pathogenesis of IBD. Many previous studies have focused on the mechanisms that miRNAs use to regulate inflammation, immunity, and microorganisms in IBD. The review highlights in detail the findings of miRNAs in the intestinal epithelial barrier of IBD, and focuses on their gene targets, signaling pathways associated with IBD, and some potential therapies. It will be beneficial for the elucidation of the interaction between miRNAs and the intestinal epithelial barrier in IBD and provide a theoretical reference for preventing and treating IBD in the future.
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Affiliation(s)
- Xiangjun Xiao
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Daiwen Chen
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
| | - Jianping Wang
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Chengdu, China
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Mohammad Rahimi H, Yadegar A, Asadzadeh Aghdaei H, Mirjalali H, Zali MR. Modulation of microRNAs and claudin-7 in Caco-2 cell line treated with Blastocystis sp., subtype 3 soluble total antigen. BMC Microbiol 2022; 22:111. [PMID: 35459091 PMCID: PMC9027909 DOI: 10.1186/s12866-022-02528-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 04/13/2022] [Indexed: 12/15/2022] Open
Abstract
Background Blastocystis sp., is a eukaryote of the large intestine, which is reported from almost all countries. The pathogenesis of this protist is not clear. The current study aimed to analyze the effects of Blastocystis sp., ST3 soluble total antigen (B3STA) on the microRNAs (miRNAs) involved in the gut permeability and also pro-inflammatory cytokines, occludin, and claudin-7. Methods Blastocystis sp., ST3 isolated from stool sample was purified, and its soluble total antigen was extracted using freeze and thawing. The Caco-2 cell line was treated with B3STA for 24 h and the expression levels of mir-16, mir-21, mir-29a, mir-223, and mir-874 were analyzed. In addition, the expression levels of il-8, il-15, occludin, and claudin-7 genes were assessed. Results B3STA significantly upregulated the expression of mir-223, and mir-874, and downregulated mir-29a. The expression of mir-16 and mir-21 was not significant. In addition, the expression of il-8 and il-15 was not significant. B3STA significantly decreased the expression level of claudin-7 (P-value < 0.0001), but the expression of occludin was not significant. Our results showed significant correlation between all studied miRNAs, except mir-29a, with downregulation of claudin-7. Conclusions This is the first study investigating the effects of Blastocystis sp., ST3 isolated from symptomatic subjects on the expression levels of miRNAs involved in the gut permeability. Our results demonstrated that B3STA may change miRNA expression, which are involved in the gut barrier integrity, and downregulates claudin-7, which is known as sealing factor.
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Affiliation(s)
- Hanieh Mohammad Rahimi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Ren Y, Feng J, Lin Y, Reinach PS, Liu Y, Xia X, Ma X, Chen W, Zheng Q. MiR-223 inhibits hyperosmolarity-induced inflammation through downregulating NLRP3 activation in human corneal epithelial cells and dry eye patients. Exp Eye Res 2022; 220:109096. [DOI: 10.1016/j.exer.2022.109096] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/29/2022] [Accepted: 04/21/2022] [Indexed: 01/10/2023]
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Donda K, Torres BA, Maheshwari A. Non-coding RNAs in Neonatal Necrotizing Enterocolitis. NEWBORN 2022; 1:120-130. [PMID: 35754997 PMCID: PMC9219563 DOI: 10.5005/jp-journals-11002-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Keyur Donda
- Department of Pediatrics, University of South Florida Health Morsani College of Medicine, Tampa, Florida, United States of America
| | - Benjamin A Torres
- Department of Pediatrics, University of South Florida Health Morsani College of Medicine, Tampa, Florida, United States of America
| | - Akhil Maheshwari
- Global Newborn Society, Clarksville, Maryland, United States of America
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Lian H, Zhong XS, Xiao Y, Sun Z, Shen Y, Zhao K, Ma X, Li Y, Niu Q, Liu M, Powell DW, Liu C, Li Q. Exosomal miR-29b of Gut Origin in Patients With Ulcerative Colitis Suppresses Heart Brain-Derived Neurotrophic Factor. Front Mol Biosci 2022; 9:759689. [PMID: 35274002 PMCID: PMC8902158 DOI: 10.3389/fmolb.2022.759689] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 01/21/2022] [Indexed: 01/13/2023] Open
Abstract
Background and Aims: While the interplay between heart and gut in inflammatory bowel disease (IBD) has previously been noted, how the inflamed gut impairs heart function remain elusive. We hypothesized that exosomal miRNAs of gut origin induce cardiac remodeling in IBD. Our aim was to identify plasma exosomal miRNAs that not only are of diagnostic value but also contribute to cardiac remodeling in patients with ulcerative colitis (UC).Methods: Plasma exosomes were isolated from UC patients and healthy control subjects and exosomal miRNAs were profiled by next-generation sequencing. Exosomal miR-29b levels in CCD841 CoN colon epithelial cells were detected by RT-qPCR. Exosomes packaged with miR-29b were incubated with H9c2 cells or administered to live mice.Results: The plasma exosomal miRNA profiles of the UC patients were significantly different from that of the controls and 20 miRNAs including miR-29b were differentially expressed. In CCD841 CoN cells, TNFα, IL-1β, and H2O2 significantly elevated miR-29b in both the cells and their secreted exosomes (p < 0.01), suggesting that intestinal epithelium secrets exosomes rich in miR-29b in IBD. In H9c2 myoblast cells, miR-29b modulated multiple genes including brain-derived neurotrophic factor (BDNF). Epithelial cell-derived exosomes packaged with miR-29b also attenuated BDNF and increased cleaved caspase 3, suggestive of apoptosis. Furthermore, tail vein injection of engineered exosomes with high levels of miR-29b suppressed BDNF and augmented cleaved caspase 3 in the heart of adult mouse (p < 0.01).Conclusion: Plasma exosomal miRNA profile could be a novel diagnostic approach for IBD. Excessive plasma exosomal miR-29b suppresses critical proteins like BDNF in IBD, leading to cardiac impairment.
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Affiliation(s)
- Haifeng Lian
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
- *Correspondence: Haifeng Lian, ; Qingjie Li,
| | - Xiaoying S. Zhong
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Ying Xiao
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhe Sun
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Yuanyuan Shen
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Kaile Zhao
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Xingbin Ma
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Yanmin Li
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Qiong Niu
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Max Liu
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Don W. Powell
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
| | - Chengxia Liu
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Qingjie Li
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States
- *Correspondence: Haifeng Lian, ; Qingjie Li,
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Vike NL, Bari S, Stetsiv K, Walter A, Newman S, Kawata K, Bazarian JJ, Martinovich Z, Nauman EA, Talavage TM, Papa L, Slobounov SM, Breiter HC. A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality. iScience 2022; 25:103483. [PMID: 35106455 PMCID: PMC8786649 DOI: 10.1016/j.isci.2021.103483] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 09/23/2021] [Accepted: 11/19/2021] [Indexed: 12/06/2022] Open
Abstract
Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites always mediated the statistical relationship between miRNAs and VR-based motor control (pSobelperm≤ 0.05; total effect > 50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes.
Permutation-based mediation statistics can be applied to multi-scale biology problems Fatty acids were a critical link between elevated miRNAs and motor control HAEs interacted with pre-season metabolite levels to model post-season levels Together, our observations point to brain-related mitochondrial dysfunction
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Affiliation(s)
- Nicole L Vike
- Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Sumra Bari
- Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Khrystyna Stetsiv
- Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Alexa Walter
- Department of Kinesiology, Pennsylvania State University, University Park, PA 16801, USA
| | - Sharlene Newman
- Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA
| | - Keisuke Kawata
- Department of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN 47405, USA.,Program in Neuroscience, College of Arts and Sciences, Indiana University, Bloomington, IN 47405, USA
| | - Jeffrey J Bazarian
- Department of Emergency Medicine, University of Rochester, Rochester, NY 14627, USA
| | - Zoran Martinovich
- Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Eric A Nauman
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.,School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA.,Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA
| | - Thomas M Talavage
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.,School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN 47907, USA.,Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45221, USA
| | - Linda Papa
- Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL 32806, USA
| | - Semyon M Slobounov
- Department of Kinesiology, Pennsylvania State University, University Park, PA 16801, USA
| | - Hans C Breiter
- Warren Wright Adolescent Center Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.,Laboratory of Neuroimaging and Genetics, Department of Psychiatry, Massachusetts General Hospital and Harvard School of Medicine, Boston, MA 02114, USA
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Cai L, Lai D, Gao J, Wu H, Shi B, Ji H, Tou J. The role and mechanisms of miRNA in neonatal necrotizing enterocolitis. Front Pediatr 2022; 10:1053965. [PMID: 36518784 PMCID: PMC9742607 DOI: 10.3389/fped.2022.1053965] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 11/03/2022] [Indexed: 11/29/2022] Open
Abstract
Neonatal necrotizing enterocolitis (NEC), the most significant causes of neonatal mortality, is a disease of acute intestinal inflammation. At present, it is not clear exactly how the disease is caused, but it has been suggested that this disorder is a result of a complex interaction among prematurity, enteral feeding and inappropriate pro-inflammation response and bacterial infection of the intestine. A microRNA (miRNA) is a class of endogenous non-coding single-stranded RNA that is about 23 nucleotides long engaging in the regulation of the gene expression. Recently, numerous studies have determined that abnormal miRNA expression plays important roles in various diseases, including NEC. Here, we summarized the role of miRNAs in NEC. We introduce the biosynthetic and function of miRNAs and then describe the possible mechanisms of miRNAs in the initiation and development of NEC, including their influence on the intestinal epithelial barrier's function and regulation of the inflammatory process. Finally, this review aids in a comprehensive understanding of the current miRNA to accurately predict the diagnosis of NEC and provide ideas to find potential therapeutic targets of miRNA for NEC. In conclusion, our aims are to highlight the close relationship between miRNAs and NEC and to summarize the practical value of developing diagnostic biomarkers and potential therapeutic targets of NEC.
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Affiliation(s)
- Linghao Cai
- Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Dengming Lai
- Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Jiafang Gao
- Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Hao Wu
- Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Bo Shi
- Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Haosen Ji
- Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Jinfa Tou
- Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
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Chen P, Huang S, Yu Q, Chao K, Wang Y, Zhou G, Zhuang X, Zeng Z, Chen M, Zhang S. Serum exosomal microRNA-144-3p: a promising biomarker for monitoring Crohn's disease. Gastroenterol Rep (Oxf) 2021; 10:goab056. [PMID: 35382172 PMCID: PMC8973006 DOI: 10.1093/gastro/goab056] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/09/2021] [Accepted: 10/10/2021] [Indexed: 12/13/2022] Open
Abstract
Background Crohn’s disease (CD) has a tendency for recurrence and requires adequate monitoring and personalized treatment. Since endoscopy is considerably invasive, serum biomarkers are required as alternatives for CD monitoring. Toward this, exosomal microRNAs (miRNAs) may serve as promising candidates. In this study, we aimed to assess the role of serum exosomal microRNA-144-3p (miR-144-3p) as a biomarker for CD monitoring. Methods We prospectively recruited 154 patients without a history of surgery (Cohort 1) and 75 patients who were to undergo intestinal resection (Cohort 2). Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination. The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction (PCR). Correlations between relative exosomal miR-144-3p levels, disease activity, and disease behavior were analysed. The area under the receiver-operating characteristic curve (AUC) was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and post-operative recurrence. Results A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls (P < 0.001). The exosomal miR-144-3p levels were positively correlated with the simple endoscopic score of CD (ρ = 0.547, P < 0.001) as well as the Rutgeerts score (ρ = 0.478, P < 0.001). Elevated exosomal miR-144-3p levels were correlated with the penetrating disease with high specificity (100% [95% confidence interval, 95.1%–100%]). The accuracy of exosomal miR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein (CRP) (AUC, 0.775 vs 0.639; P < 0.001). Conclusions Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD. It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.
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Affiliation(s)
- Peng Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Shanshan Huang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Qiao Yu
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, P. R. China
| | - Kang Chao
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Ying Wang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Gaoshi Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Xiaojun Zhuang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Zhirong Zeng
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Shenghong Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
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The Impact of MicroRNAs during Inflammatory Bowel Disease: Effects on the Mucus Layer and Intercellular Junctions for Gut Permeability. Cells 2021; 10:cells10123358. [PMID: 34943865 PMCID: PMC8699384 DOI: 10.3390/cells10123358] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/23/2021] [Accepted: 11/25/2021] [Indexed: 12/15/2022] Open
Abstract
Research on inflammatory bowel disease (IBD) has produced mounting evidence for the modulation of microRNAs (miRNAs) during pathogenesis. MiRNAs are small, non-coding RNAs that interfere with the translation of mRNAs. Their high stability in free circulation at various regions of the body allows researchers to utilise miRNAs as biomarkers and as a focus for potential treatments of IBD. Yet, their distinct regulatory roles at the gut epithelial barrier remain elusive due to the fact that there are several external and cellular factors contributing to gut permeability. This review focuses on how miRNAs may compromise two components of the gut epithelium that together form the initial physical barrier: the mucus layer and the intercellular epithelial junctions. Here, we summarise the impact of miRNAs on goblet cell secretion and mucin structure, along with the proper function of various junctional proteins involved in paracellular transport, cell adhesion and communication. Knowledge of how this elaborate network of cells at the gut epithelial barrier becomes compromised as a result of dysregulated miRNA expression, thereby contributing to the development of IBD, will support the generation of miRNA-associated biomarker panels and therapeutic strategies that detect and ameliorate gut permeability.
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Host miRNA and immune cell interactions: relevance in nano-therapeutics for human health. Immunol Res 2021; 70:1-18. [PMID: 34716546 DOI: 10.1007/s12026-021-09247-8] [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: 06/18/2021] [Accepted: 10/11/2021] [Indexed: 12/15/2022]
Abstract
Around 2200 miRNA (microRNA) genes were found in the human genome. miRNAs are arranged in clusters within the genome and share the same transcriptional regulatory units. It has been revealed that approximately 50% of miRNAs elucidated in the genome are transcribed from non-protein-coding genes, and the leftover miRNAs are present in the introns of coding sequences. We are now approaching a stage in which miRNA diagnostics and therapies can be established confidently, and several commercial efforts are underway to carry these innovations from the bench to the clinic. MiRNAs control many of the significant cellular activities such as production, differentiation, growth, and metabolism. Particularly in the immune system, miRNAs have emerged as a crucial biological component during diseased state and homeostasis. miRNAs have been found to regulate inflammatory responses and autoimmune disorders. Moreover, each miRNA targets multiple genes simultaneously, making miRNAs promising tools as diagnostic biomarkers and as remedial targets. Still, one of the major obstacles in miRNA-based approaches is the achievement of specific and efficient systemic delivery of miRNAs. To overcome these challenges, nanoformulations have been synthesized to protect miRNAs from degradation and enhance cellular uptake. The current review deals with the miRNA-mediated regulation of the recruitment and activation of immune cells, especially in the tumor microenvironment, viral infection, inflammation, and autoimmunity. The nano-based miRNA delivery modes are also discussed here, especially in the context of immune modulation.
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Moret-Tatay I, Cerrillo E, Hervás D, Iborra M, Sáez-González E, Forment J, Tortosa L, Nos P, Gadea J, Beltrán B. Specific Plasma MicroRNA Signatures in Predicting and Confirming Crohn's Disease Recurrence: Role and Pathogenic Implications. Clin Transl Gastroenterol 2021; 12:e00416. [PMID: 34695034 PMCID: PMC8547914 DOI: 10.14309/ctg.0000000000000416] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 08/22/2021] [Indexed: 01/09/2023] Open
Abstract
INTRODUCTION MicroRNAs (miRNAs) are important epigenetic regulators in Crohn's disease (CD); however, their contribution to postoperative recurrence (POR) is still unknown. We aimed to characterize the potential role of miRNAs in predicting POR in patients with CD and to identify their pathogenic implications. METHODS Of 67 consecutively operated patients with CD, we included 44 with pure ileal CD. Peripheral blood samples were taken before surgery and during follow-up. The patients were classified according to the presence or absence of POR assessed by ileocolonoscopy or magnetic resonance imaging enterography. The miRNAs were profiled by reverse transcription polymerase chain reaction before surgery and during morphological POR or, for those who remained in remission, 1 year after surgery. R software and mirWalk were used. RESULTS Five human miRNAs (miR-191-5p, miR-15b-5p, miR-106b-5p, miR-451a, and miR-93-5p) were selected for discriminating between the 2 patient groups at presurgery (PS), with an area under the curve of 0.88 (95% confidence interval [0.79, 0.98]). Another 5 (miR-15b-5p, miR-451a, miR-93-5p, miR-423-5p, and miR-125b-5p) were selected for 1 year, with an area under the curve of 0.96 (95% confidence interval [0.91, 1.0]). We also created nomograms for POR risk estimation. CCND2 and BCL9L genes were related to PS miRNA profiles; SENP5 and AKT3 genes were related to PS and 1 year; and SUV39H1 and MAPK3K10 were related to 1 year. DISCUSSION Different plasma miRNA signatures identify patients at high POR risk, which could help optimize patient outcomes. We developed nomograms to facilitate the clinical use of these results. The identified miRNAs participate in apoptosis, autophagy, proinflammatory immunological T-cell clusters, and reactive oxygen species metabolism.
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Affiliation(s)
- Inés Moret-Tatay
- Inflammatory Bowel Disease Research Group, Health Research Institute, Hospital La Fe (IIS La Fe), Valencia, Spain
- Biomedical Research Centre, Hepatic and Digestive Diseases Network [Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)], Madrid, Spain
| | - Elena Cerrillo
- Inflammatory Bowel Disease Research Group, Health Research Institute, Hospital La Fe (IIS La Fe), Valencia, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - David Hervás
- Biostatistics Unit, Health Research IIS La Fe, Valencia, Spain
| | - Marisa Iborra
- Inflammatory Bowel Disease Research Group, Health Research Institute, Hospital La Fe (IIS La Fe), Valencia, Spain
- Biomedical Research Centre, Hepatic and Digestive Diseases Network [Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)], Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Esteban Sáez-González
- Inflammatory Bowel Disease Research Group, Health Research Institute, Hospital La Fe (IIS La Fe), Valencia, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Javier Forment
- The Institute for Plant Molecular and Cellular Biology (IBMCP), Polytechnic University of Valencia- Spanish Research Council (CSIC), Valencia, Spain
| | - Luis Tortosa
- Inflammatory Bowel Disease Research Group, Health Research Institute, Hospital La Fe (IIS La Fe), Valencia, Spain
- Biomedical Research Centre, Hepatic and Digestive Diseases Network [Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)], Madrid, Spain
| | - Pilar Nos
- Inflammatory Bowel Disease Research Group, Health Research Institute, Hospital La Fe (IIS La Fe), Valencia, Spain
- Biomedical Research Centre, Hepatic and Digestive Diseases Network [Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)], Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - Jose Gadea
- The Institute for Plant Molecular and Cellular Biology (IBMCP), Polytechnic University of Valencia- Spanish Research Council (CSIC), Valencia, Spain
| | - Belén Beltrán
- Inflammatory Bowel Disease Research Group, Health Research Institute, Hospital La Fe (IIS La Fe), Valencia, Spain
- Biomedical Research Centre, Hepatic and Digestive Diseases Network [Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)], Madrid, Spain
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
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Tang Y, Kline KT, Zhong XS, Xiao Y, Lian H, Peng J, Liu X, Powell DW, Tang G, Li Q. Chronic colitis upregulates microRNAs suppressing brain-derived neurotrophic factor in the adult heart. PLoS One 2021; 16:e0257280. [PMID: 34543287 PMCID: PMC8452076 DOI: 10.1371/journal.pone.0257280] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 08/28/2021] [Indexed: 01/08/2023] Open
Abstract
Ulcerative colitis and Crohn's disease are classified as chronic inflammatory bowel diseases (IBD) with known extraintestinal manifestations. The interplay between heart and gut in IBD has previously been noted, but the mechanisms remain elusive. Our objective was to identify microRNAs mediating molecular remodeling and resulting cardiac impairment in a rat model of colitis. To induce chronic colitis, dextran sodium sulfate (DSS) was given to adult rats for 5 days followed by 9 days with normal drinking water for 4 cycles over 8 weeks. Echocardiography was performed to evaluate heart function. DSS-induced colitis led to a significant decrease in ejection fraction, increased left ventricular mass and size, and elevated B-type natriuretic protein. MicroRNA profiling showed a total of 56 miRNAs significantly increased in the heart by colitis, 8 of which are predicted to target brain-derived neurotrophic factor (BDNF). RT-qPCR validated the increases of miR-1b, Let-7d, and miR-155. Transient transfection revealed that miR-155 significantly suppresses BDNF in H9c2 cells. Importantly, DSS colitis markedly decreased BDNF in both myocardium and serum. Levels of various proteins critical to cardiac homeostasis were also altered. Functional studies showed that BDNF increases cell viability and mitigates H2O2-induced oxidative damage in H9c2 cells, demonstrating its protective role in the adult heart. Mechanistically, cellular experiments identified IL-1β as the inflammatory mediator upregulating cardiac miR-155; this effect was confirmed in adult rats. Furthermore, IL-1β neutralizing antibody ameliorated the DSS-induced increase in miR-155 and concurrent decrease in BDNF in the adult heart, showing therapeutic potential. Our findings indicate that chronic colitis impairs heart function through an IL-1β→miR-155→BDNF signaling axis.
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Affiliation(s)
- Yanbo Tang
- Department of Gastroenterology, the First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Kevin T. Kline
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States of America
| | - Xiaoying S. Zhong
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States of America
| | - Ying Xiao
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States of America
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Haifeng Lian
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, China
| | - Jun Peng
- Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China
| | - Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Don W. Powell
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States of America
| | - Guodu Tang
- Department of Gastroenterology, the First Affiliated Hospital, Guangxi Medical University, Nanning, China
| | - Qingjie Li
- Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, United States of America
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Prabhu SR, Ware AP, Saadi AV. Erythrocyte miRNA regulators and malarial pathophysiology. INFECTION GENETICS AND EVOLUTION 2021; 93:105000. [PMID: 34252617 DOI: 10.1016/j.meegid.2021.105000] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/18/2021] [Accepted: 07/08/2021] [Indexed: 11/24/2022]
Abstract
Pathophysiology of Plasmodium falciparum and Plasmodium vivax in malaria vis a vis host and the parasite genome interactions has been deciphered recently to present the biology of cerebral malaria, severe anaemia and placental malaria. Small non-coding RNAs have exhibited their potential to be considered as indicators and regulators of diseases. The malarial pathologies and their associated mechanisms mediated by miRNAs and their role in haematopoiesis and red cell-related disorders are elucidated. Evidence of miRNA carrying exosome-like vesicles released during infection, delivering signals to endothelial cells enhancing gene expression, resulting in parasite sequestration and complications leading to pathologies of cerebral malaria are important breakthroughs. Pregnancy malaria showed Plasmodium surface antigen promoted erythrocyte sequestration in the placental intervillous space, provoking disease development and assorted complications. Syncytiotrophoblast-derived microparticles during pregnancy and fetus development may predict pathophysiological progression on account of their altered miRNA cargoes in malaria.
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Affiliation(s)
- Sowmya R Prabhu
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Akshay P Ware
- Department of Bioinformatics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Abdul Vahab Saadi
- Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
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Mastiha has efficacy in immune-mediated inflammatory diseases through a microRNA-155 Th17 dependent action. Pharmacol Res 2021; 171:105753. [PMID: 34224858 DOI: 10.1016/j.phrs.2021.105753] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/30/2021] [Accepted: 06/30/2021] [Indexed: 02/08/2023]
Abstract
Mastiha is a natural nutritional supplement with known anti-inflammatory properties. Non-alcoholic fatty liver disease (NAFLD) and Inflammatory bowel disease (IBD) are immune mediated inflammatory diseases that share common pathophysiological features. Mastiha has shown beneficial effects in both diseases. MicroRNAs have emerged as key regulators of inflammation and their modulation by phytochemicals have been extensively studied over the last years. Therefore, the aim of this study was to investigate whether a common route exists in the anti-inflammatory activity of Mastiha, specifically through the regulation of miRNA levels. Plasma miR-16, miR-21 and miR-155 were measured by Real-Time PCR before and after two double blinded and placebo-controlled randomized clinical trials with Mastiha. In IBD and particularly in ulcerative colitis patients in relapse, miR-155 increased in the placebo group (p = 0.054) whereas this increase was prevented by Mastiha. The mean changes were different in the two groups even after adjusting for age, sex and BMI (p = 0.024 for IBD and p = 0.042). Although the results were not so prominent in NAFLD, miR-155 displayed a downward trend in the placebo group (p = 0.054) whereas the levels did not changed significantly in the Mastiha group in patients with less advanced fibrosis. Our results propose a regulatory role for Mastiha in circulating levels of miR-155, a critical player in T helper-17 (Th17) differentiation and function.
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43
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Santonocito S, Polizzi A, Palazzo G, Isola G. The Emerging Role of microRNA in Periodontitis: Pathophysiology, Clinical Potential and Future Molecular Perspectives. Int J Mol Sci 2021; 22:5456. [PMID: 34064286 PMCID: PMC8196859 DOI: 10.3390/ijms22115456] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/17/2021] [Accepted: 05/21/2021] [Indexed: 02/07/2023] Open
Abstract
During the last few decades, it has been established that messenger ribonucleic acid (mRNA) transcription does not inevitably lead to protein translation, but there are numerous processes involved in post-transcriptional regulation, which is a continuously developing field of research. MicroRNAs (miRNAs) are a group of small non-coding RNAs, which negatively regulate protein expression and are implicated in several physiological and pathological mechanisms. Aberrant expression of miRNAs triggers dysregulation of multiple cellular processes involved in innate and adaptive immune responses. For many years, it was thought that miRNAs acted only within the cell in which they were synthesised, but, recently, they have been found outside cells bound to lipids and proteins, or enclosed in extracellular vesicles, namely exosomes. They can circulate throughout the body, transferring information between cells and altering gene expression in the recipient cells, as they can fuse with and be internalised by the recipient cells. Numerous studies on miRNAs have been conducted in order to identify possible biomarkers that can be used in the diagnosis of periodontal disease. However, as therapeutic agents, single miRNAs can target several genes and influence multiple regulatory networks. The aim of this review was to examine the molecular role of miRNAs and exosomes in the pathophysiology of periodontal disease and to evaluate possible clinical and future implications for a personalised therapeutical approach.
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Affiliation(s)
| | | | | | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy; (S.S.); (A.P.); (G.P.)
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44
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Jung H, Kim JS, Lee KH, Tizaoui K, Terrazzino S, Cargnin S, Smith L, Koyanagi A, Jacob L, Li H, Hong SH, Yon DK, Lee SW, Kim MS, Wasuwanich P, Karnsakul W, Shin JI, Kronbichler A. Roles of microRNAs in inflammatory bowel disease. Int J Biol Sci 2021; 17:2112-2123. [PMID: 34131410 PMCID: PMC8193269 DOI: 10.7150/ijbs.59904] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 05/08/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.
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Affiliation(s)
- HyunTaek Jung
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae Seok Kim
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Keum Hwa Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kalthoum Tizaoui
- Laboratory Microorganisms and Active Biomolecules, Sciences Faculty of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Salvatore Terrazzino
- Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy
| | - Sarah Cargnin
- Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Novara, Italy
| | - Lee Smith
- The Cambridge Centre for Sport and Exercise Science, Anglia Ruskin University, Cambridge, CB1 1PT, UK
| | - Ai Koyanagi
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830 Barcelona, Spain.,ICREA, Pg. Lluis Companys 23, 08010 Barcelona, Spain
| | - Louis Jacob
- Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, 08830 Barcelona, Spain.,Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, 78000 Versailles, France
| | - Han Li
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Sung Hwi Hong
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Keon Yon
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung Won Lee
- Department of Data Science, Sejong University College of Software Convergence, Seoul, Republic of Korea
| | - Min Seo Kim
- Korea University, College of Medicine, Seoul, Republic of Korea
| | - Paul Wasuwanich
- University of Florida College of Medicine, Gainesville, FL 32610, USA
| | - Wikrom Karnsakul
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Jae Il Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Andreas Kronbichler
- Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria
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Jonaitis P, Kiudelis V, Streleckiene G, Gedgaudas R, Skieceviciene J, Kupcinskas J. Novel Biomarkers in the Diagnosis of Benign and Malignant Gastrointestinal Diseases. Dig Dis 2021; 40:1-13. [PMID: 33647906 DOI: 10.1159/000515522] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/26/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Various noninvasive biomarkers have been used in the diagnosis, prognosis, and treatment of different gastrointestinal (GI) diseases for years. Novel technological developments and profound perception of molecular processes related to GI diseases over the last decade have allowed researchers to evaluate genetic, epigenetic, and many other potential molecular biomarkers in different diseases and clinical settings. Here, we present a review of recent and most relevant articles in order to summarize major findings on novel biomarkers in the diagnosis of benign and malignant GI diseases. SUMMARY Genetic variations, noncoding RNAs (ncRNAs), cell-free DNA (cfDNA), and microbiome-based biomarkers have been extensively analyzed as potential biomarkers in benign and malignant GI diseases. Multiple single-nucleotide polymorphisms have been linked with a number of GI diseases, and these observations are further being used to build up disease-specific genetic risk scores. Micro-RNAs and long ncRNAs have a large potential as noninvasive biomarkers in the management of inflammatory bowel diseases and GI tumors. Altered microbiome profiles were observed in multiple GI diseases, but most of the findings still lack translational clinical application. As of today, cfDNA appears to be the most potent biomarker for early detection and screening of GI cancers. Key Messages: Novel noninvasive molecular biomarkers show huge potential as useful tools in the diagnostics and management of different GI diseases. However, the use of these biomarkers in real-life clinical practice still remains limited, and further large studies are needed to elucidate the ultimate role of these potential noninvasive clinical tools.
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Affiliation(s)
- Paulius Jonaitis
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Vytautas Kiudelis
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Greta Streleckiene
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Rolandas Gedgaudas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Jurgita Skieceviciene
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Juozas Kupcinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
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Malham M, James JP, Jakobsen C, Hoegdall E, Holmstroem K, Wewer V, Nielsen BS, Riis LB. Mucosal microRNAs relate to age and severity of disease in ulcerative colitis. Aging (Albany NY) 2021; 13:6359-6374. [PMID: 33647883 PMCID: PMC7993741 DOI: 10.18632/aging.202715] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 01/25/2021] [Indexed: 12/12/2022]
Abstract
Despite significant evidence that the expression of several microRNAs (miRNAs) impacts disease activity in patients with ulcerative colitis (UC), it remains unknown if the more severe disease phenotype seen in pediatric onset UC can be explained by an altered miRNA expression. In this study, we assessed the relationship between miRNA expression, age, and disease severity in pediatric and adult patients with UC. Using RT-qPCR, we analyzed the expression of miR-21, miR-31, miR-126, miR-142 and miR-155 in paraffin embedded rectum biopsies from 30 pediatric and 30 adult-onset UC patients. We found that lesions from adult patients had significantly higher expression levels of miR-21 compared to pediatric patients and that the expression levels of miR-31 (all patients) and miR-155 (pediatric patients only) correlated inversely with histological assessed disease severity. Using in situ hybridization followed by image analysis, the expression level estimates of miR-21 and miR-126 correlated with histological assessed disease severity. In conclusion, we found that the expression of miRNAs depends on the age of the patient and/or the severity of the disease, suggesting that miRNAs may contribute to the regulation of inflammation in UC and could be useful biomarkers in the surveillance of disease severity.
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Affiliation(s)
- Mikkel Malham
- The Pediatric Department, Copenhagen University Hospital, Hvidovre 2650, Denmark.,The Pediatric Department, Holbaek Hospital, Holbaek 4300, Denmark
| | - Jaslin P James
- Department of Pathology, Copenhagen University Hospital, Herlev 2730, Denmark.,Biomedical Technology, Bioneer A/S, Hoersholm 2970, Denmark
| | - Christian Jakobsen
- The Pediatric Department, Copenhagen University Hospital, Hvidovre 2650, Denmark
| | - Estrid Hoegdall
- Department of Pathology, Copenhagen University Hospital, Herlev 2730, Denmark
| | - Kim Holmstroem
- Biomedical Technology, Bioneer A/S, Hoersholm 2970, Denmark
| | - Vibeke Wewer
- The Pediatric Department, Copenhagen University Hospital, Hvidovre 2650, Denmark
| | - Boye S Nielsen
- Biomedical Technology, Bioneer A/S, Hoersholm 2970, Denmark
| | - Lene B Riis
- Department of Pathology, Copenhagen University Hospital, Herlev 2730, Denmark
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Zhang H, Fu T, Zhang C. MicroRNA-1249 Targets G Protein Subunit Alpha 11 and Facilitates Gastric Cancer Cell Proliferation, Motility and Represses Cell Apoptosis. Onco Targets Ther 2021; 14:1249-1259. [PMID: 33658793 PMCID: PMC7917321 DOI: 10.2147/ott.s272599] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 01/22/2021] [Indexed: 12/27/2022] Open
Abstract
Aim The purpose of our study was to investigate the effects of miR-1249 in gastric cancer. Methods By analyzing the data obtained from TCGA database, the expression and prognosis of miR-1249 in gastric cancer patients were analyzed. Then, CCK8, colony forming and transwell assays were used to test cell proliferation and motility. The cell apoptosis was detected by flow cytometry. The Pearson correlation coefficient analyzed was applied to analyze the correlation between GNA11 and miR-1249. qRT-PCR and Western blotting assays were employed to detect the mRNA and protein levels. Results We discovered that miR-1249 was highly expressed and was associated with a worse prognosis in gastric cancer patients. Besides, miR-1249 was up-regulated in gastric cancer cell lines (AGS, MKN45 and SNU1). More interestingly, miR-1249 exerted facilitating impacts on gastric cancer cell proliferation and motility, whereas miR-1249 acted as a suppressing effect on gastric cancer apoptosis. G protein subunit alpha 11 (GNA11) was a target gene of miR-1249 and was negatively correlated with miR-1249. Furthermore, GNA11 was negatively regulated by miR-1249. Additionally, GNA11 was lowly expressed in gastric cancer tissues and cell lines, as well as low GNA11 expression, was related to poor overall survival results in gastric cancer patients. The promoting influences of miR-1249 over-expression on AGS cell proliferation and motility was rescued by GNA11 over-expression, which might be achieved by regulating PI3K/AKT/mTOR signalling pathway. Conclusion Above all, we concluded that miR-1249 was concerned with the progression of gastric cancer through regulating GNA11, suggesting that miR-1249 and GNA11 might serve as predictive biomarkers for gastric cancer therapy.
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Affiliation(s)
- Hongzhu Zhang
- Department of Gastroenterology, Jinan Jigang Hospital, Jinan, Shandong, 250101, People's Republic of China
| | - Tingting Fu
- Department of Gastroenterology, Jinan Jigang Hospital, Jinan, Shandong, 250101, People's Republic of China
| | - Cuiping Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People's Republic of China
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Abstract
Inflammatory bowel disease (IBD) as a chronic inflammation in colon and small intestine has two subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Genome studies have shown that UC and CD are related to microRNAs (miRNAs) expression in addition to environmental factors. This article reviews important researches that have recently been done on miRNAs roles in CD and UC disease. First, miRNA is introduced and its biogenesis and function are discussed. Afterward, roles of miRNAs in inflammatory processes involved in IBD are showed. Finally, this review proposes some circulating and tissue-specific miRNAs, which are useful for CD and UC fast diagnosis and grade prediction. As a conclusion, miRNAs are efficient diagnostic molecules especially in IBD subtypes discrimination and can be used by microarray and real time PCR methods for disease detection and classification.
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miR-362-3p Targets Orosomucoid 1 to Promote Cell Proliferation, Restrain Cell Apoptosis and Thereby Mitigate Hypoxia/Reoxygenation-Induced Cardiomyocytes Injury. Cardiovasc Toxicol 2021; 21:387-398. [PMID: 33459949 DOI: 10.1007/s12012-020-09631-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 12/30/2020] [Indexed: 12/21/2022]
Abstract
This study aimed to investigate the mechanism of how miR-362-3p/orosomucoid 1 (ORM1) involved in hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury. Based on data obtained from Gene Expression Omnibus (GEO) database, we revealed that ORM1 was highly expressed and positively correlated with the expression of inflammatory factors (MAPK1, MAPK3, IL1B and CASP9). miR-362-3p was identified as an upstream regulatory miRNA of ORM1 and negatively modulated the mRNA and protein expression levels of ORM1 in H/R-injured cardiomyocytes. Moreover, we found that miR-362-3p was downregulated in cardiomyocytes injured by H/R. The promoting influence of miR-362-3p mimic on the proliferation and the inhibitory effect of miR-362-3p mimic on the apoptosis of H/R-stimulated cardiomyocytes were eliminated by overexpression of ORM1. Furthermore, miR-362-3p affected the expression of MAPK1, MAPK3, IL1B and CASP9 in H/R-injured cardiomyocytes through targeting ORM1. Our outcomes illustrated that miR-362-3p exhibited a protective influence on H/R-induced cardiomyocytes through targeting ORM1.
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50
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MicroRNA Biomarkers in IBD-Differential Diagnosis and Prediction of Colitis-Associated Cancer. Int J Mol Sci 2020; 21:ijms21217893. [PMID: 33114313 PMCID: PMC7660644 DOI: 10.3390/ijms21217893] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). These are chronic autoimmune diseases of unknown etiology affecting the gastrointestinal tract. The IBD population includes a heterogeneous group of patients with varying disease courses requiring personalized treatment protocols. The complexity of the disease often delays the diagnosis and the initiation of appropriate treatments. In a subset of patients, IBD leads to colitis-associated cancer (CAC). MicroRNAs are single-stranded regulatory noncoding RNAs of 18 to 22 nucleotides with putative roles in the pathogenesis of IBD and colorectal cancer. They have been explored as biomarkers and therapeutic targets. Both tissue-derived and circulating microRNAs have emerged as promising biomarkers in the differential diagnosis and in the prognosis of disease severity of IBD as well as predictive biomarkers in drug resistance. In addition, knowledge of the cellular localization of differentially expressed microRNAs is a prerequisite for deciphering the biological role of these important epigenetic regulators and the cellular localization may even contribute to an alternative repertoire of biomarkers. In this review, we discuss findings based on RT-qPCR, microarray profiling, next generation sequencing and in situ hybridization of microRNA biomarkers identified in the circulation and in tissue biopsies.
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