Volume 11, Issue 4 (Vol.11 No.4 Jan 2023)                   rbmb.net 2023, 11(4): 614-625 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Abdelgwad M, Zakaria R, Marzouk S, Sabry D, Ahmed R, Badary H A et al . The Emerging Role of Circular RNA Homeodomain Interacting Protein Kinase 3 and Circular RNA 0046367 through Wnt/Beta-Catenin Pathway on the Pathogenesis of Nonalcoholic Steatohepatitis in Egyptian Patients. rbmb.net 2023; 11 (4) :614-625
URL: http://rbmb.net/article-1-1052-en.html
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Egypt.
Abstract:   (1782 Views)
Background: Non-alcoholic fatty liver disease is a major problem worldwide that needs non-invasive biomarkers for early diagnosis and treatment response assessment. We aimed to assess the correlation between circRNA-HIPK3 and miRNA-29a expression and its role as miRNA-29a sponge, as well as the correlation between circRNA-0046367 and miRNA-34a expression and its role as miRNA-34a sponge and their effect on regulation of the Wnt/β catenin pathway, which may provide a new target for treatment of non-alcoholic steatohepatitis.
Methods: the research was performed on 110 participants: group (I): fifty-five healthy donors served as controls and group (II): fifty-five patients with fatty liver pattern on abdominal ultrasound. Lipid profile and liver functions were assessed. RT-PCR was performed to assess the RNAs: circRNA-HIPK3, circRNA-0046367, miRNA-29a, miRNA-34a and Wnt mRNA gene expression. ELISA was performed to determine β-catenin protein levels.

Results: miRNA-34a and circRNA-HIPK3 expression were significantly greater, while miRNA-29a and circRNA-0046367 expression were significantly less, in patients than in controls. Wnt/β-catenin regulated by miRNA-29a and miRNA-34a showed a significant decrease that leads to its abnormal effect on lipid metabolism.

Conclusions: our results imply that miRNA-29a can be investigated as a target for circRNA-HIPK3, while miRNA-34a can be investigated as a target for circRNA-0046367, and that circRNA-HIPK3 and circRNA-0046367 may have emerging roles that can affect the pathogenesis of nonalcoholic steatohepatitis through the Wnt/β-catenin pathway and thus be used as therapeutic targets for the disease.
Full-Text [PDF 377 kb]   (1302 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2022/09/22 | Accepted: 2022/11/10 | Published: 2023/04/3

1. Younossi Z, Tacke F, Arrese M, Chander Sharma B, Mostafa I, Bugianesi E, et al. Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology. 2019;69(6):2672-2682. [DOI:10.1002/hep.30251] [PMID]
2. Bessone F, Razori MV, Roma MG. Molecular pathways of nonalcoholic fatty liver disease development and progression. Cell Mol Life Sci. 2019;76(1):99-128. [DOI:10.1007/s00018-018-2947-0] [PMID]
3. Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010;1803(11):1231-43. [DOI:10.1016/j.bbamcr.2010.06.013] [PMID]
4. Xin S, Zhan Q, Chen X, Xu J, Yu Y. Efficacy of serum miRNA test as a non-invasive method to diagnose nonalcoholic steatohepatitis: a systematic review and meta-analysis. BMC Gastroenterol. 2020;20(1):186. [DOI:10.1186/s12876-020-01334-8] [PMID] [PMCID]
5. Tian M, Chen R, Li T, Xiao B. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance. J Clin Lab Anal. 2018;32(3):e22281. [DOI:10.1002/jcla.22281] [PMID] [PMCID]
6. Fu L, Jiang Z, Li T, Hu Y, Guo J. Circular RNAs in hepatocellular carcinoma: Functions and implications. Cancer Med. 2018;7:3101-3109. [DOI:10.1002/cam4.1574] [PMID] [PMCID]
7. Guo XY, Chen JN, Sun F, Wang YQ, Pan Q, Fan JG. circRNA_0046367 Prevents Hepatoxicity of Lipid Peroxidation: An Inhibitory Role against Hepatic Steatosis. Oxid Med Cell Longev. 2017;2017:3960197. [DOI:10.1155/2017/3960197] [PMID] [PMCID]
8. Guo XY, Sun F, Chen JN, Wang YQ, Pan Q, Fan JG. circRNA_ 0046366 inhibits
9. hepatocellular steatosis by normalization of PPAR signaling. World J Gastroenterol. 2018;24(3):323-337. [DOI:10.3748/wjg.v24.i3.323] [PMID] [PMCID]
10. Fan Y, Zheng Y, Wang J, Zhao T, Liang T. Differential expression and bioinformatic analysis of circRNA in nonalcoholic steatohepatitis cirrhosis. Int J Clin Exp Pathol. 2020;13(11):2820-2830.
11. Saad El-Din S, Ahmed Rashed L, Eissa M, Eldemery AB, Abdelkareem Mohammed O, Abdelgwad M. Potential Role of circRNA-HIPK3/microRNA-124a Crosstalk in the Pathogenesis of Rheumatoid Arthritis. Rep Biochem Mol Biol. 2022;10(4):527-536. [DOI:10.52547/rbmb.10.4.527] [PMID] [PMCID]
12. Monga SP. β-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis. Gastroenterology. 2015;148(7):1294-310. [DOI:10.1053/j.gastro.2015.02.056] [PMID] [PMCID]
13. Bayatiani MR, Ahmadi A, Aghabozorgi R, Seif F. Concomitant Up-Regulation of Hsa- Mir-374 and Down-Regulation of Its Targets, GSK-3β and APC, in Tissue Samples of Colorectal Cancer. Rep Biochem Mol Biol. 2021;9(4):408-416. [DOI:10.52547/rbmb.9.4.408] [PMID] [PMCID]
14. Chan YH. Biostatistics 102: quantitative data--parametric & non-parametric tests. Singapore Med J. 2003;44(8):391-6.
15. Tanaka N, Kimura T, Fujimori N, Nagaya T, Komatsu M, Tanaka E. Current status, problems, and perspectives of non-alcoholic fatty liver disease research. World J Gastroenterol. 2019;25(2):163-177. [DOI:10.3748/wjg.v25.i2.163] [PMID] [PMCID]
16. Liu J, Xiao Y, Wu X, Jiang L, Yang S, Ding Z, et al. A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis. BMC Genomics. 2018;19(1):188. [DOI:10.1186/s12864-018-4575-3] [PMID] [PMCID]
17. Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197-206. [DOI:10.1038/nature14177] [PMID] [PMCID]
18. Gastaldelli A, Cusi K. From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options. JHEP Rep. 2019;1(4):312-328. [DOI:10.1016/j.jhepr.2019.07.002] [PMID] [PMCID]
19. Dharmalingam M, Yamasandhi P. Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. Indian J Endocrinol Metab. 2018; 22(3): 421-428. [DOI:10.4103/ijem.IJEM_585_17] [PMID] [PMCID]
20. Ioannou GN. The Role of Cholesterol in the Pathogenesis of NASH. Trends Endocrinol Metab. 2016;27(2):84-95. [DOI:10.1016/j.tem.2015.11.008] [PMID]
21. Verma S, Jensen D, Hart J, Mohanty SR. Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). Liver Int. 2013;33(9):1398-405. [DOI:10.1111/liv.12226] [PMID]
22. Thong VD, Quynh BTH. Correlation of Serum Transaminase Levels with Liver Fibrosis Assessed by Transient Elastography in Vietnamese Patients with Nonalcoholic Fatty Liver Disease. Int J Gen Med. 2021;14:1349-1355. [DOI:10.2147/IJGM.S309311] [PMID] [PMCID]
23. Pulzi FB, Cisternas R, Melo MR, Ribeiro CM, Malheiros CA, Salles JE. New clinical score to diagnose nonalcoholic steatohepatitis in obese patients. Diabetol Metab Syndr. 2011;3(1):3. [DOI:10.1186/1758-5996-3-3] [PMID] [PMCID]
24. Fujii H, Doi H, Ko T, Fukuma T, Kadono T, Asaeda K, et al. Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study. BMC Gastroenterol. 2020;20(1):217. [DOI:10.1186/s12876-020-01369-x] [PMID] [PMCID]
25. Arif KMT, Elliott EK, Haupt LM, Griffiths LR. Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets. Cancers (Basel). 2020;12(10):2922. [DOI:10.3390/cancers12102922] [PMID] [PMCID]
26. Ceccarelli S, Panera N, Gnani D, Nobili V. Dual role of microRNAs in NAFLD. Int J Mol Sci. 2013; 14(4): 8437-8455. [DOI:10.3390/ijms14048437] [PMID] [PMCID]
27. Karimi-Sales E, Jeddi S, Ebrahimi-Kalan A, Alipour MR. Protective Role of trans-Chalcone against the Progression from Simple Steatosis to Non-alcoholic Steatohepatitis: Regulation of miR-122, 21, 34a, and 451. Adv Pharm Bull. 2022;12(1):200-205. [DOI:10.34172/apb.2022.022] [PMID] [PMCID]
28. Lin HY, Wang FS, Yang YL, Huang YH. MicroRNA-29a Suppresses CD36 to Ameliorate High Fat Diet-Induced Steatohepatitis and Liver Fibrosis in Mice. Cells. 2019;8(10):1298. [DOI:10.3390/cells8101298] [PMID] [PMCID]
29. Lin HY, Yang YL, Wang PW, Wang FS, Huang YH. The Emerging Role of MicroRNAs in NAFLD: Highlight of MicroRNA-29a in Modulating Oxidative Stress, Inflammation, and Beyond. Cells. 2020;9(4):1041. [DOI:10.3390/cells9041041] [PMID] [PMCID]
30. Yang YL, Wang PW, Wang FS, Lin HY,
31. Huang YH. miR-29a Modulates GSK3β/SIRT1-Linked Mitochondrial Proteostatic Stress to Ameliorate Mouse Non-Alcoholic Steatohepatitis. Int J Mol Sci. 2020;21(18):6884. [DOI:10.3390/ijms21186884] [PMID] [PMCID]
32. Behari J, Yeh TH, Krauland L, Otruba W, Cieply B, Hauth B, et al. Liver-specific beta-catenin knockout mice exhibit defective bile acid and cholesterol homeostasis and increased susceptibility to diet-induced steatohepatitis. Am J Pathol. 2010;176(2):744-53. [DOI:10.2353/ajpath.2010.090667] [PMID] [PMCID]
33. Clarke JD, Novak P, Lake AD, Shipkova P, Aranibar N, Robertson D, et al. Characterization of hepatocellular carcinoma related genes and metabolites in human nonalcoholic fatty liver disease. Dig Dis Sci. 2014;59(2):365-74. [DOI:10.1007/s10620-013-2873-9] [PMID] [PMCID]
34. El-Derany MO, El-Demerdash E. Pyrvinium pamoate attenuates non-alcoholic steatohepatitis: Insight on hedgehog/Gli and Wnt/β-catenin signaling crosstalk. Biochem Pharmacol. 2020;177:113942. [DOI:10.1016/j.bcp.2020.113942] [PMID]
35. Russell JO, Monga SP. Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology. Annu Rev Pathol. 2018;13:351-378. [DOI:10.1146/annurev-pathol-020117-044010] [PMID] [PMCID]
36. Zhou W, Cai Z, Liu J, Wang D, Ju H, Xu R. Circular RNA: metabolism, functions and interactions with proteins. Mol Cancer.2020;19:172. [DOI:10.1186/s12943-020-01286-3] [PMID] [PMCID]
37. Chien Y, Tsai PH, Lai YH, Lu KH, Liu CY, Lin HF, et al. CircularRNA as novel biomarkers in liver diseases. J Chin Med Assoc. 2020;83(1):15-17. [DOI:10.1097/JCMA.0000000000000230] [PMID]
38. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215. [DOI:10.1038/ncomms11215] [PMID] [PMCID]
39. Le LT, Swingler TE, Crowe N, Vincent TL, Barter MJ, Donell ST, et al. The microRNA-29 family in cartilage homeostasis and osteoarthritis. J Mol Med (Berl). 2016;94(5):583-96. [DOI:10.1007/s00109-015-1374-z] [PMID] [PMCID]
40. Huang X, Chen Z, Shi W, Zhang R, Li L, Liu H, et al. TMF inhibits miR-29a/Wnt/β-catenin signaling through upregulating Foxo3a activity in osteoarthritis chondrocytes. Drug Des Devel Ther. 2019;13:2009-2019. [DOI:10.2147/DDDT.S209694] [PMID] [PMCID]
41. Zhao C, Miao Y, Cao Z, Shi J, Li J, Kang F, et al. MicroRNA-29b regulates hypertrophy of murine mesenchymal stem cells induced toward chondrogenesis. J Cell Biochem. 2019;120(5): 8742-8753. [DOI:10.1002/jcb.28161] [PMID]
42. Cheng C, Qin Y, Zhi Q, Wang J, Qin C. Knockdown of long non-coding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3K/Akt and Wnt/β-catenin signaling pathways by up-regulating miR-34a. Int J Biol Macromol. 2018;107:2620-2629. [DOI:10.1016/j.ijbiomac.2017.10.154] [PMID]

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb