دورية أكاديمية
أعرض في EDS

Analysis of the therapeutic potential of miR-124 and miR-16 in non-alcoholic fatty liver disease.

التفاصيل البيبلوغرافية
العنوان: Analysis of the therapeutic potential of miR-124 and miR-16 in non-alcoholic fatty liver disease.
المؤلفون: Mahmoudi A; Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., Jalili A; Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: jalilia@mums.ac.ir., Aghaee-Bakhtiari SH; Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Bioinformatics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran., Oskuee RK; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Targeted Drug Delivery Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran., Butler AE; Research Department, Royal College of Surgeons in Ireland, Bahrain, Adliya, Bahrain., Rizzo M; School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Italy; Department of Biochemistry, Mohamed Bin Rashid University, Dubai, United Arab Emirates., Sahebkar A; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amir_saheb2000@yahoo.com.
المصدر: Journal of diabetes and its complications [J Diabetes Complications] 2024 Apr; Vol. 38 (4), pp. 108722. Date of Electronic Publication: 2024 Mar 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Pub. Co Country of Publication: United States NLM ID: 9204583 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-460X (Electronic) Linking ISSN: 10568727 NLM ISO Abbreviation: J Diabetes Complications Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Elsevier Science Pub. Co., c1992-
مواضيع طبية MeSH: Non-alcoholic Fatty Liver Disease*/genetics , Non-alcoholic Fatty Liver Disease*/metabolism , MicroRNAs*/genetics , MicroRNAs*/metabolism , Azo Compounds*, Humans ; Oleic Acid/metabolism ; Oleic Acid/pharmacology ; Oleic Acid/therapeutic use ; Toll-Like Receptor 4 ; Lipid Metabolism/genetics ; Liver/metabolism
مستخلص: Backgrounds: Non-alcoholic fatty liver disease (NAFLD) is a common condition affecting >25 % of the population worldwide. This disorder ranges in severity from simple steatosis (fat accumulation) to severe steatohepatitis (inflammation), fibrosis and, at its end-stage, liver cancer. A number of studies have identified overexpression of several key genes that are critical in the initiation and progression of NAFLD. MiRNAs are potential therapeutic agents that can regulate several genes simultaneously. Therefore, we transfected cell lines with two key miRNAs involved in targeting NAFLD-related genes.
Methods: The suppression effects of the investigated miRNAs (miR-124 and miR-16) and genes (TNF, TLR4, SCD, FASN, SREBF2, and TGFβ-1) from our previous study were investigated by real-time PCR in Huh7 and HepG2 cells treated with oleic acid. Oil red O staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were utilized to assess cell lipid accumulation and cytotoxic effects of the miRNAs, respectively. The pro-oxidant-antioxidant balance (PAB) assay was undertaken for miR-16 and miR-124 after cell transfection.
Results: Following transfection of miRNAs into HepG2, oil red O staining showed miR-124 and miR-16 reduced oleic acid-induced lipid accumulation by 35.2 % and 28.6 % respectively (p < 0.05). In Huh7, miR-124 and miR-16 reduced accumulation by 23.5 % and 31.3 % respectively (p < 0.05) but without impacting anti-oxidant activity. Real-time PCR in HepG2 revealed miR-124 decreased expression of TNF by 0.13-fold, TLR4 by 0.12-fold and SREBF2 by 0.127-fold (p < 0.05). miR-16 decreased TLR4 by 0.66-fold and FASN by 0.3-fold (p < 0.05). In Huh7, miR-124 decreased TNF by 0.12-fold and FASN by 0.09-fold (p < 0.05). miR-16 decreased SCD by 0.28-fold and FASN by 0.64-fold (p < 0.05). MTT assays showed, in HepG2, viability was decreased 24.7 % by miR-124 and decreased 33 % by miR-16 at 72 h (p < 0.05). In Huh7, miR-124 decreased viability 42 % at 48 h and 29.33 % at 72 h (p < 0.05), while miR-16 decreased viability by 32.3 % (p < 0.05).
Conclusion: These results demonstrate the ability of miR-124 and miR-16 to significantly reduce lipid accumulation and expression of key pathogenic genes associated with NAFLD through direct targeting. Though this requires further in vivo investigation.
Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: NAFLD; Real-time PCR; Transfection; miR-124; miR-16
المشرفين على المادة: 2UMI9U37CP (Oleic Acid)
G7S71FND9B (oil red O)
0 (Toll-Like Receptor 4)
0 (MicroRNAs)
0 (MIRN124 microRNA, human)
0 (MIRN16 microRNA, human)
0 (Azo Compounds)
تواريخ الأحداث: Date Created: 20240319 Date Completed: 20240401 Latest Revision: 20240508
رمز التحديث: 20240508
DOI: 10.1016/j.jdiacomp.2024.108722
PMID: 38503000
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-460X
DOI:10.1016/j.jdiacomp.2024.108722