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CLINICAL RESEARCH
CircBAZ1B stimulates myocardial ischemia/reperfusion injury (MI/RI) by modulating miR-1252-5p/ATF3-mediated ferroptosis
1
Department of Cardiovascular Medicine, Zibo Central Hospital, Zibo, Shandong, China
Submission date: 2024-01-10
Final revision date: 2024-02-22
Acceptance date: 2024-02-22
Online publication date: 2024-08-16
Corresponding author
Xiqian Wang
Department of Cardiovascular Medicine, Zibo Central Hospital, Zibo, Shandong 255000, China., China
Department of Cardiovascular Medicine, Zibo Central Hospital, Zibo, Shandong 255000, China., China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Circular RNAs (circRNAs) have been implicated in myocardial ischemia (MI)/reperfusion injury (RI), yet their essential roles in MI/RI-induced ferroptosis have not been fully elucidated. Here, we focused on the biological function and regulatory mechanism of circBAZ1B, a circRNA derived from the bromodomain adjacent to the zinc finger domain 1B (BAZ1B) gene, in MI/RI progression.
Material and methods:
We used a rat model for MI/RI, assessing myocardial infarct size via electrocardiogram (ECG) and histological staining (hematoxylin and eosin [H&E] and 2,3,5-triphenyltetrazolium chloride [TTC]). Rat cardiomyoblasts (H9c2) were used for in vitro hypoxia-reoxygenation (H/R) cell model construction. Cell viability, apoptosis, lipid reactive oxygen species (ROS) levels and iron content were determined via Cell Counting Kit-8 (CCK-8) and flow cytometric assays. Gene and ferroptosis-related protein expression levels were verified by qRT‒PCR and Western blotting. RNA pull-down, RNA immunoprecipitation (RIP), and a dual-luciferase reporter system were utilized for verification of the molecular interactions.
Results:
The results showed that MI/RI was accompanied by ferroptosis. We also found that activating transcription factor 3 (ATF3) knockdown promoted myocardial cell viability and inhibited ferroptosis. Notably, activation of ATF3 transcription was demonstrated to upregulate the expression of its downstream target ACSL4. Functional analysis indicated that circBAZ1B promoted ATF3 expression via miR-1252-5p. In vivo experimental data further revealed that circBAZ1B suppressed cardiomyocyte activity and promoted ferroptosis, thereby facilitating MI/RI progression.
Conclusions:
The circBAZ1B/miR-1252-5p/ATF3 axis is crucial in MI/RI pathogenesis through ferroptosis regulation, offering a potential therapeutic target. Inhibiting this pathway may alleviate MI/RI effects, suggesting the need for further clinical studies.
Circular RNAs (circRNAs) have been implicated in myocardial ischemia (MI)/reperfusion injury (RI), yet their essential roles in MI/RI-induced ferroptosis have not been fully elucidated. Here, we focused on the biological function and regulatory mechanism of circBAZ1B, a circRNA derived from the bromodomain adjacent to the zinc finger domain 1B (BAZ1B) gene, in MI/RI progression.
Material and methods:
We used a rat model for MI/RI, assessing myocardial infarct size via electrocardiogram (ECG) and histological staining (hematoxylin and eosin [H&E] and 2,3,5-triphenyltetrazolium chloride [TTC]). Rat cardiomyoblasts (H9c2) were used for in vitro hypoxia-reoxygenation (H/R) cell model construction. Cell viability, apoptosis, lipid reactive oxygen species (ROS) levels and iron content were determined via Cell Counting Kit-8 (CCK-8) and flow cytometric assays. Gene and ferroptosis-related protein expression levels were verified by qRT‒PCR and Western blotting. RNA pull-down, RNA immunoprecipitation (RIP), and a dual-luciferase reporter system were utilized for verification of the molecular interactions.
Results:
The results showed that MI/RI was accompanied by ferroptosis. We also found that activating transcription factor 3 (ATF3) knockdown promoted myocardial cell viability and inhibited ferroptosis. Notably, activation of ATF3 transcription was demonstrated to upregulate the expression of its downstream target ACSL4. Functional analysis indicated that circBAZ1B promoted ATF3 expression via miR-1252-5p. In vivo experimental data further revealed that circBAZ1B suppressed cardiomyocyte activity and promoted ferroptosis, thereby facilitating MI/RI progression.
Conclusions:
The circBAZ1B/miR-1252-5p/ATF3 axis is crucial in MI/RI pathogenesis through ferroptosis regulation, offering a potential therapeutic target. Inhibiting this pathway may alleviate MI/RI effects, suggesting the need for further clinical studies.
REFERENCES (47)
1.
Zhang Y, Zhang Y, Zang J, et al. Pharmaceutical therapies for necroptosis in myocardial ischemia–reperfusion injury. J Cardiovasc Develop Dis 2023; 10: 303.
2.
Toldo S, Abbate A. The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases. Nat Rev Cardiol 2024; 21: 219-37.
3.
Toldo S, Mauro AG, Cutter Z, et al. Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2018; 315: H1553-68.
4.
Wang R, Chen X, Li X, et al. Molecular therapy of cardiac ischemia–reperfusion injury based on mitochondria and ferroptosis. J Mol Med 2023; 101: 1059-71.
5.
Yu Y, Yan Y, Niu F, et al. Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases. Cell Death Discov 2021; 7: 193.
6.
Hu H, Chen Y, Jing L, et al. The link between ferroptosis and cardiovascular diseases: a novel target for treatment. Front Cardiovasc Med 2021; 8: 710963.
7.
Capelletti MM, Manceau H, Puy H, et al. Ferroptosis in liver diseases: an overview. Int J Mol Sci 2020; 21 20200711.
8.
Mou Y, Wang J, Wu J, et al. Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J Hematol Oncol 2019; 12: 34.
9.
Weiland A, Wang Y, Wu W, et al. Ferroptosis and its role in diverse brain diseases. Mol Neurobiol 2019; 56: 4880-93.
10.
Ajoolabady A, Aslkhodapasandhokmabad H, Libby P, et al. Ferritinophagy and ferroptosis in the management of metabolic diseases. Trends Endocrinol Metab 2021; 32: 444-62.
11.
Yan HF, Zou T, Tuo QZ, et al. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther 2021; 6: 49.
12.
Chen X, Kang R, Kroemer G, et al. Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol 2021; 18: 280-96.
13.
Wu Y, Zhang S, Gong X, et al. The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression. Mol Cancer 2020; 19: 39.
14.
Yue H, Zhan Y, Zhang Z, et al. The emerging role of ferroptosis in myocardial fibrosis of atrial fibrillation. Arch Med Sci 2023; 19: 507-12.
15.
Zhao WK, Zhou Y, Xu TT, et al. Ferroptosis: opportunities and challenges in myocardial ischemia-reperfusion injury. Oxid Med Cell Longev 2021; 2021: 9929687.
16.
Lillo-Moya J, Rojas-Sole C, Munoz-Salamanca D, et al. Targeting ferroptosis against ischemia/reperfusion cardiac injury. Antioxidants 2021; 10: 667.
17.
Li X, Ma N, Xu J, et al. Targeting ferroptosis: pathological mechanism and treatment of ischemia-reperfusion injury. Oxid Med Cell Longev 2021; 2021: 1587922.
18.
Wu X, Li Y, Zhang S, et al. Ferroptosis as a novel therapeutic target for cardiovascular disease. Theranostics 2021; 11: 3052-9.
19.
Liu K, Chen S, Lu R. Identification of important genes related to ferroptosis and hypoxia in acute myocardial infarction based on WGCNA. Bioengineered 2021; 12: 7950-63.
20.
Li Y, Pan D, Wang X, et al. Silencing ATF3 might delay tbhp-induced intervertebral disc degeneration by repressing npc ferroptosis, apoptosis, and ECM degradation. Oxid Med Cell Longev 2022; 2022: 4235126.
21.
Saaoud F, Drummer IVC, Shao Y, et al. Circular RNAs are a novel type of non-coding RNAs in ROS regulation, cardiovascular metabolic inflammations and cancers. Pharmacol Ther 2021; 220: 107715.
22.
Tang X, Ren H, Guo M, et al. Review on circular RNAs and new insights into their roles in cancer. Comput Struct Biotechnol J 2021; 19: 910-28.
23.
Li C, Ni YQ, Xu H, et al. Roles and mechanisms of exosomal non-coding RNAs in human health and diseases. Signal Transduct Target Ther 2021; 6: 383.
24.
Huang Y, Zhang C, Xiong J, et al. Emerging important roles of circRNAs in human cancer and other diseases. Genes Dis 2021; 8: 412-23.
25.
Yang Y, Tai W, Lu N, et al. lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis. Aging (Albany NY) 2020; 12: 9085-102.
26.
Ni T, Huang X, Pan S, et al. Inhibition of the long non-coding RNA ZFAS1 attenuates ferroptosis by sponging miR-150-5p and activates CCND2 against diabetic cardiomyopathy. J Cell Mol Med 2021; 25: 9995-10007.
27.
Wang M, Mao C, Ouyang L, et al. Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA. Cell Death Differ 2019; 26: 2329-43.
28.
Liu XS, Yang JW, Zeng J, et al. SLC2A1 is a diagnostic biomarker involved in immune infiltration of colorectal cancer and associated with m6A modification and ceRNA. Front Cell Dev Biol 2022; 10: 853596.
29.
Bazhabayi M, Qiu X, Li X, et al. CircGFRA1 facilitates the malignant progression of HER-2-positive breast cancer via acting as a sponge of miR-1228 and enhancing AIFM2 expression. J Cell Mol Med 2021; 25: 10248-56.
30.
Ye X, Hang Y, Lu Y, et al. CircRNA circ-NNT mediates myocardial ischemia/reperfusion injury through activating pyroptosis by sponging miR-33a-5p and regulating USP46 expression. Cell Death Discov 2021; 7: 370.
31.
Liu G, Zhang BF, Hu Q, et al. Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3beta signaling pathway. Biochem Biophys Res Commun 2020; 531: 242-9.
32.
Liang W, Guo J, Li J, et al. Downregulation of miR-122 attenuates hypoxia/reoxygenation (H/R)-induced myocardial cell apoptosis by upregulating GATA-4. Biochem Biophys Res Commun 2016; 478: 1416-22.
33.
Ye Z, Hu Q, Zhuo Q, et al. Abrogation of ARF6 promotes RSL3-induced ferroptosis and mitigates gemcitabine resistance in pancreatic cancer cells. Am J Cancer Res 2020; 10: 1182-93.
34.
Li JY, Liu SQ, Yao RQ, et al. A novel insight into the fate of cardiomyocytes in ischemia-reperfusion injury: from iron metabolism to ferroptosis. Front Cell Dev Biol 2021; 9: 799499.
35.
Wang K, Li Y, Qiang T, et al. Role of epigenetic regulation in myocardial ischemia/reperfusion injury. Pharmacol Res 2021; 170: 105743.
36.
Bugger H, Pfeil K. Mitochondrial ROS in myocardial ischemia reperfusion and remodeling. Biochim Biophys Acta Mol Basis Dis 2020; 1866: 165768.
37.
Casin KM, Calvert JW. Dynamic regulation of cysteine oxidation and phosphorylation in myocardial ischemia-reperfusion injury. Cells 2021; 10: 2388.
38.
Yang M, Linn BS, Zhang Y, et al. Mitophagy and mitochondrial integrity in cardiac ischemia-reperfusion injury. Biochim Biophys Acta Mol Basis Dis 2019; 1865: 2293-302.
39.
Carbonell T, Gomes AV. MicroRNAs in the regulation of cellular redox status and its implications in myocardial ischemia-reperfusion injury. Redox Biol 2020; 36: 101607.
40.
Altesha MA, Ni T, Khan A, et al. Circular RNA in cardiovascular disease. J Cell Physiol 2019; 234: 5588-600.
41.
Marinescu MC, Lazar AL, Marta MM, et al. Non-coding RNAs: prevention, diagnosis, and treatment in myocardial ischemia-reperfusion injury. Int J Mol Sci 2022; 23: 2728.
42.
Xue Y, Wu T, Sheng Y, et al. MicroRNA-1252-5p, regulated by Myb, inhibits invasion and epithelial-mesenchymal transition of pancreatic cancer cells by targeting NEDD9. Aging (Albany NY) 2021; 13: 18924-45.
43.
Gu ZR, Liu W. The LncRNA AL161431.1 targets miR-1252-5p and facilitates cellular proliferation and migration via MAPK signaling in endometrial carcinoma. Eur Rev Med Pharmacol Sci 2020; 24: 2294-302..
44.
Rodrigues-Junior DM, Pelarin MFA, Nader HB, et al. MicroRNA-1252-5p associated with extracellular vesicles enhances bortezomib sensitivity in multiple myeloma cells by targeting heparanase. Onco Targets Ther 2021; 14: 455-67.
45.
Chen X, Chen H, Liu M, et al. Long noncoding RNA LINC00520 accelerates lung adenocarcinoma progression via miR-1252-5p/FOXR2 pathway. Hum Cell 2021; 34: 478-90.
46.
Sharma P, Wang X, Ming CLC, et al. Considerations for the bioengineering of advanced cardiac in vitro models of myocardial infarction. Small 2021; 17: e2003765.
47.
Kumar M, Kasala ER, Bodduluru LN, et al. Animal models of myocardial infarction: mainstay in clinical translation. Regul Toxicol Pharmacol 2016; 76: 221-30.
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| ISSN: | 1734-1922 |
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