Top

Published in:

01-04-2022

Circ-SWT1 Ameliorates H₂O₂-Induced Apoptosis, Oxidative Stress and Endoplasmic Reticulum Stress in Cardiomyocytes via miR-192-5p/SOD2 Axis

Authors: Song Chen, Lixiu Sun, Min Hao, Xian Liu

Published in: Cardiovascular Toxicology | Issue 4/2022

Abstract

Acute myocardial infarction (AMI) is a most serious cardiovascular disease. Increasing findings have indicated that circular RNAs (circRNAs) serve as competent biomarkers in the process of AMI. Herein, our study aimed to probe the functions of circ-SWT1 in cardiomyocyte injury after AMI. H₂O₂-induced human cardiomyocyte cell line AC16 were used for expression and function analyses. The levels of genes and proteins were detected by qRT-PCR and western blotting. Cell apoptosis was analyzed by flow cytometry and caspase3 activity analysis. The oxidative stress injury was evaluated by detecting the levels of reactive oxygen species (ROS), malondialdehyde and superoxide dismutase (SOD). Western blotting was used to detect the expressions of apoptosis-related markers and endoplasmic reticulum stress (ERS) markers. Dual-luciferase reporter, RIP and pull-down assays were applied to confirm the interaction between miR-192-5p and circ-SWT1 or SOD2. H₂O₂ treatment significantly decreased circ-SWT1 expression in cardiomyocytes, functionally, ectopic expression of circ-SWT1 attenuated H₂O₂-triggered apoptosis, oxidative stress and endoplasmic reticulum (ER) stress in cardiomyocytes in vitro. Mechanistically, circ-SWT1 competitively bound to miR-192-5p to relieve the repression of miR-192-5p on its target SOD2. Further rescue experiments showed that miR-192-5p upregulation reversed the inhibitory effects of circ-SWT1 on H₂O₂-induced cardiomyocyte injury. Moreover, miR-192-5p inhibition protected cardiomyocytes against H₂O₂-evoked apoptosis, oxidative stress and ER stress, which were abolished by SOD2 silencing. Circ-SWT1 ameliorates H₂O₂-induced apoptosis, oxidative stress and ER stress in cardiomyocytes via miR-192-5p/SOD2 axis, suggesting the potential involvement of circ-SWT1 in AMI process.

Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R., de Ferranti, S. D., Floyd, J., Fornage, M., Gillespie, C., Isasi, C. R., Jiménez, M. C., Jordan, L. C., Judd, S. E., Lackland, D., Lichtman, J. H., Lisabeth, L., Liu, S., Longenecker, C. T., … Muntner, P. (2017). Heart disease and stroke statistics-2017 update: A report from the American Heart Association. Circulation, 135(10), e146–e603. https://doi.org/10.1161/cir.0000000000000485CrossRefPubMedPubMedCentral

Ramachandra, C. J. A., Hernandez-Resendiz, S., Crespo-Avilan, G. E., Lin, Y. H., & Hausenloy, D. J. (2020). Mitochondria in acute myocardial infarction and cardioprotection. EBioMedicine. https://doi.org/10.1016/j.ebiom.2020.102884CrossRefPubMedPubMedCentral

Li, M., Tang, X., Liu, X., Cui, X., Lian, M., Zhao, M., Peng, H., & Han, X. (2020). Targeted miR-21 loaded liposomes for acute myocardial infarction. Journal of Materials Chemistry B, 8(45), 10384–10391. https://doi.org/10.1039/d0tb01821jCrossRefPubMed

Neri, M., Fineschi, V., Di Paolo, M., Pomara, C., Riezzo, I., Turillazzi, E., & Cerretani, D. (2015). Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction. Current Vascular Pharmacology, 13(1), 26–36. https://doi.org/10.2174/15701611113119990003CrossRefPubMed

Rong, X., Ge, D., Yu, L., Li, L., Chu, M., & Lv, H. (2020). Enalapril attenuates endoplasmic reticulum stress and mitochondrial injury induced by myocardial infarction via activation of the TAK1/NFAT pathway in mice. Experimental and Therapeutic Medicine, 19(2), 972–980. https://doi.org/10.3892/etm.2019.8280CrossRefPubMed

Chen, L. L., & Yang, L. (2015). Regulation of circRNA biogenesis. RNA Biology, 12(4), 381–388. https://doi.org/10.1080/15476286.2015.1020271CrossRefPubMedPubMedCentral

Rybak-Wolf, A., Stottmeister, C., Glažar, P., Jens, M., Pino, N., Giusti, S., Hanan, M., Behm, M., Bartok, O., Ashwal-Fluss, R., Herzog, M., Schreyer, L., Papavasileiou, P., Ivanov, A., Öhman, M., Refojo, D., Kadener, S., & Rajewsky, N. (2015). Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Molecular cell, 58(5), 870–885. https://doi.org/10.1016/j.molcel.2015.03.027CrossRefPubMed

Kristensen, L. S., Andersen, M. S., Stagsted, L. V. W., Ebbesen, K. K., Hansen, T. B., & Kjems, J. (2019). The biogenesis, biology and characterization of circular RNAs. Nature Reviews. Genetics, 20(11), 675–691. https://doi.org/10.1038/s41576-019-0158-7CrossRefPubMed

Wu, J., Qi, X., Liu, L., Hu, X., Liu, J., Yang, J., Yang, J., Lu, L., Zhang, Z., Ma, S., Li, H., Yun, X., Sun, T., Wang, Y., Wang, Z., Liu, Z., & Zhao, W. (2019). Emerging epigenetic regulation of circular RNAs in human cancer. Molecular Therapy. Nucleic Acids, 16, 589–596. https://doi.org/10.1016/j.omtn.2019.04.011CrossRefPubMedPubMedCentral

10.

Marques-Rocha, J. L., Samblas, M., Milagro, F. I., Bressan, J., Martínez, J. A., & Marti, A. (2015). Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB Journal, 29(9), 3595–3611. https://doi.org/10.1096/fj.14-260323CrossRefPubMed

11.

Bai, M., Pan, C. L., Jiang, G. X., & Zhang, Y. M. (2020). CircRNA 010567 improves myocardial infarction rats through inhibiting TGF-β1. European Review for Medical and Pharmacological Sciences, 24(1), 369–375. https://doi.org/10.26355/eurrev_202001_19935CrossRefPubMed

12.

Zhang, M., Wang, Z., Cheng, Q., Wang, Z., Lv, X., Wang, Z., & Li, N. (2020). Circular RNA (circRNA) CDYL induces myocardial regeneration by ceRNA after myocardial infarction. Medical Science Monitor, 4, 3. https://doi.org/10.12659/msm.923188CrossRef

13.

Zhao, C., Liu, J., Ge, W., Li, Z., Lv, M., Feng, Y., Liu, X., Liu, B., & Zhang, Y. (2020). Identification of regulatory circRNAs involved in the pathogenesis of acute myocardial infarction. Frontiers in Genetics. https://doi.org/10.3389/fgene.2020.626492CrossRefPubMedPubMedCentral

14.

Liu, C., Liu, Y., & Yang, Z. (2014). Myocardial infarction induces cognitive impairment by increasing the production of hydrogen peroxide in adult rat hippocampus. Neuroscience Letters, 560, 112–116. https://doi.org/10.1016/j.neulet.2013.12.027CrossRefPubMed

15.

Salmena, L., Poliseno, L., Tay, Y., Kats, L., & Pandolfi, P. P. (2011). A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language? Cell, 146(3), 353–358. https://doi.org/10.1016/j.cell.2011.07.014CrossRefPubMedPubMedCentral

16.

Yang, R., Xing, L., Zheng, X., Sun, Y., Wang, X., & Chen, J. (2019). The circRNA circAGFG1 acts as a sponge of miR-195-5p to promote triple-negative breast cancer progression through regulating CCNE1 expression. Molecular Cancer, 18(1), 4. https://doi.org/10.1186/s12943-018-0933-7CrossRefPubMedPubMedCentral

17.

Zhai, C., Qian, G., Wu, H., Pan, H., Xie, S., Sun, Z., Shao, P., Tang, G., Hu, H., & Zhang, S. (2020). Knockdown of circ_0060745 alleviates acute myocardial infarction by suppressing NF-κB activation. Journal of Cellular and Molecular Medicine, 24(21), 12401–12410. https://doi.org/10.1111/jcmm.15748CrossRefPubMedPubMedCentral

18.

Zhao, B., Li, G., Peng, J., Ren, L., Lei, L., Ye, H., Wang, Z., & Zhao, S. (2021). CircMACF1 attenuates acute myocardial infarction through miR-500b-5p-EMP1 axis. Journal of Cardiovascular Translational Research, 14(1), 161–172. https://doi.org/10.1007/s12265-020-09976-5CrossRefPubMed

19.

Bezerra, O. C., França, C. M., Rocha, J. A., Neves, G. A., Souza, P. R. M., Teixeira Gomes, M., Malfitano, C., Loleiro, T. C. A., Dourado, P. M., Llesuy, S., de Angelis, K., Irigoyen, M. C. C., Ulloa, L., & Consolim-Colombo, F. M. (2017). Cholinergic stimulation improves oxidative stress and inflammation in experimental myocardial infarction. Scientific Reports, 7(1), 13687. https://doi.org/10.1038/s41598-017-14021-8CrossRefPubMedPubMedCentral

20.

Barrera, G. (2012). Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncology. https://doi.org/10.5402/2012/137289CrossRefPubMedPubMedCentral

21.

Mao, C., Yuan, J. Q., Lv, Y. B., Gao, X., Yin, Z. X., Kraus, V. B., Luo, J. S., Chei, C. L., Matchar, D. B., Zeng, Y., & Shi, X. M. (2019). Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: A community-based cohort study. BMC Geriatrics, 19(1), 104. https://doi.org/10.1186/s12877-019-1109-zCrossRefPubMedPubMedCentral

22.

Ochoa, C. D., Wu, R. F., & Terada, L. S. (2018). ROS signaling and ER stress in cardiovascular disease. Molecular Aspects of Medicine, 63, 18–29. https://doi.org/10.1016/j.mam.2018.03.002CrossRefPubMedPubMedCentral

23.

Li, Y., Hu, J., Li, L., Cai, S., Zhang, H., Zhu, X., Guan, G., & Dong, X. (2018). Upregulated circular RNA circ_0016760 indicates unfavorable prognosis in NSCLC and promotes cell progression through miR-1287/GAGE1 axis. Biochemical and Biophysical Research Communications, 503(3), 2089–2094. https://doi.org/10.1016/j.bbrc.2018.07.164CrossRefPubMed

24.

Zhang, Y., Huang, R., Zhou, W., Zhao, Q., & Lü, Z. (2017). miR-192–5p mediates hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes via targeting of FABP3. Journal of Biochemical and Molecular Toxicology. https://doi.org/10.1002/jbt.21873CrossRefPubMed

25.

Sun, F., Yuan, W., Wu, H., Chen, G., Sun, Y., Yuan, L., Zhang, W., & Lei, M. (2020). LncRNA KCNQ1OT1 attenuates sepsis-induced myocardial injury via regulating miR-192–5p/XIAP axis. Experimental biology and medicine (Maywood, N.J.), 245(7), 620–630. https://doi.org/10.1177/1535370220908041CrossRef

26.

Flynn, J. M., & Melov, S. (2013). SOD2 in mitochondrial dysfunction and neurodegeneration. Free Radical Biology & Medicine, 62, 4–12. https://doi.org/10.1016/j.freeradbiomed.2013.05.027CrossRef

Title: Circ-SWT1 Ameliorates H2O2-Induced Apoptosis, Oxidative Stress and Endoplasmic Reticulum Stress in Cardiomyocytes via miR-192-5p/SOD2 Axis
Authors: Song Chen
Lixiu Sun
Min Hao
Xian Liu
Publication date: 01-04-2022
Publisher: Springer US
Published in: Cardiovascular Toxicology / Issue 4/2022
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-022-09720-2

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Circ-SWT1 Ameliorates H₂O₂-Induced Apoptosis, Oxidative Stress and Endoplasmic Reticulum Stress in Cardiomyocytes via miR-192-5p/SOD2 Axis

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2022

Effects of Low- and High-Dose Valproic Acid and Lamotrigine on the Heart in Female Rats

Rosuvastatin Alleviates Coronary Microembolization-Induced Cardiac Injury by Suppressing Nox2-Induced ROS Overproduction and Myocardial Apoptosis

LncRNA HOTTIP Knockdown Attenuates Acute Myocardial Infarction via Regulating miR-92a-2/c-Met Axis

Indoxyl Sulfate Activates NLRP3 Inflammasome to Induce Cardiac Contractile Dysfunction Accompanied by Myocardial Fibrosis and Hypertrophy

Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches

AT1 Receptors: Their Actions from Hypertension to Cognitive Impairment

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page