Knockdown of CircSlc8a1 Inhibited the Ferroptosis in the Angiotensin II Treated H9c2 Cells Via MiR-673-5p/TFRC Axis

Overview

Journal J Bioenerg Biomembr

Publisher Springer

Specialties Biochemistry
Biology
Endocrinology

Date 2023 Dec 29

PMID 38158500

Authors

Kaidi Wu

Jiawei du

Affiliations

Soon will be listed here.

Abstract

Background: This study aimed to investigate the role of circSlc8a1 in cardiac hypertrophy (CH), a pathological change in various cardiovascular diseases.

Methods: An in vitro CH model was established using angiotensin II (AngII) treated H9c2 cells, followed by western blotting and RT-qPCR for detecting relative expressions. Cell viability and proliferation were analyzed using CCK-8 and EdU assays, while lactate dehydrogenase (LDH), reactive oxygen species (ROS), glutathione (GSH), and iron levels were determined using corresponding kits. Moreover, dual-luciferase reporter and RNA pull-down assays were performed to demonstrate whether miR-673-5p is bound to circSlc8a1 or transferrin receptor (TFRC).

Results: The results indicated that the expressions of circSlc8a1 and TFRC were increased, while miR-673-5p was decreased in the AngII treated H9c2 cells. The ferroptosis inhibitor treatment decreased the atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-major histocompatibility complex (β-MHC) protein expressions, and circSlc8a1 expressions. Knocking down of circSlc8a1 inhibited promoted the cell viability and proliferation, increased the GSH content, glutathione peroxidase 4, and solute carrier family 7 member 11 protein expressions, and decreased the LDH, ROS, iron levels, and RAS protein expressions. The MiR-673-5p inhibitor antagonized the role of si-circSlc8a1, and the over-expressed TFRC reversed the miR-673-5p mimicking effects in AngII treated H9c2 cells.

Conclusion: CircSlc8a1 promoted the ferroptosis in CH via regulating the miR-673-5p/TFRC axis.

References

Anandhan A, Dodson M, Schmidlin C, Liu P, Zhang D . Breakdown of an Ironclad Defense System: The Critical Role of NRF2 in Mediating Ferroptosis. Cell Chem Biol. 2020; 27(4):436-447. PMC: 7597851. DOI: 10.1016/j.chembiol.2020.03.011. View

Friedmann Angeli J, Schneider M, Proneth B, Tyurina Y, Tyurin V, Hammond V . Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014; 16(12):1180-91. PMC: 4894846. DOI: 10.1038/ncb3064. View

Geng Z, Fan W, Zhou B, Ye C, Tong Y, Zhou Y . FNDC5 attenuates obesity-induced cardiac hypertrophy by inactivating JAK2/STAT3-associated inflammation and oxidative stress. J Transl Med. 2019; 17(1):107. PMC: 6444535. DOI: 10.1186/s12967-019-1857-8. View

Huang A, Zheng H, Wu Z, Chen M, Huang Y . Circular RNA-protein interactions: functions, mechanisms, and identification. Theranostics. 2020; 10(8):3503-3517. PMC: 7069073. DOI: 10.7150/thno.42174. View

Kristensen L, Andersen M, Stagsted L, Ebbesen K, Hansen T, Kjems J . The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019; 20(11):675-691. DOI: 10.1038/s41576-019-0158-7. View

Li H, Xu J, Fang X, Zhu J, Yang J, Pan R . Circular RNA circRNA_000203 aggravates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p binding to Gata4. Cardiovasc Res. 2019; 116(7):1323-1334. PMC: 7243276. DOI: 10.1093/cvr/cvz215. View

Lu Q, Liu T, Feng H, Yang R, Zhao X, Chen W . Circular RNA circSLC8A1 acts as a sponge of miR-130b/miR-494 in suppressing bladder cancer progression via regulating PTEN. Mol Cancer. 2019; 18(1):111. PMC: 6588875. DOI: 10.1186/s12943-019-1040-0. View

Lu D, Chatterjee S, Xiao K, Riedel I, Wang Y, Foo R . MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes. J Mol Cell Cardiol. 2020; 148:46-49. PMC: 7470794. DOI: 10.1016/j.yjmcc.2020.08.017. View

Nakamura M, Sadoshima J . Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 2018; 15(7):387-407. DOI: 10.1038/s41569-018-0007-y. View

10.

Pan J, Xu Z, Guo G, Xu C, Song Z, Li K . Circ_nuclear factor I X (circNfix) attenuates pressure overload-induced cardiac hypertrophy via regulating miR-145-5p/ATF3 axis. Bioengineered. 2021; 12(1):5373-5385. PMC: 8806771. DOI: 10.1080/21655979.2021.1960462. View

11.

Proneth B, Conrad M . Ferroptosis and necroinflammation, a yet poorly explored link. Cell Death Differ. 2018; 26(1):14-24. PMC: 6294786. DOI: 10.1038/s41418-018-0173-9. View

12.

Ren Z, Yu P, Li D, Li Z, Liao Y, Wang Y . Single-Cell Reconstruction of Progression Trajectory Reveals Intervention Principles in Pathological Cardiac Hypertrophy. Circulation. 2020; 141(21):1704-1719. DOI: 10.1161/CIRCULATIONAHA.119.043053. View

13.

Seo K, Parikh V, Ashley E . Stretch-Induced Biased Signaling in Angiotensin II Type 1 and Apelin Receptors for the Mediation of Cardiac Contractility and Hypertrophy. Front Physiol. 2020; 11:181. PMC: 7082839. DOI: 10.3389/fphys.2020.00181. View

14.

Shen L, Hu Y, Lou J, Yin S, Wang W, Wang Y . CircRNA‑0044073 is upregulated in atherosclerosis and increases the proliferation and invasion of cells by targeting miR‑107. Mol Med Rep. 2019; 19(5):3923-3932. DOI: 10.3892/mmr.2019.10011. View

15.

Si X, Zheng H, Wei G, Li M, Li W, Wang H . circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a. Mol Ther Nucleic Acids. 2020; 21:636-655. PMC: 7393325. DOI: 10.1016/j.omtn.2020.06.024. View

16.

Stockwell B, Friedmann Angeli J, Bayir H, Bush A, Conrad M, Dixon S . Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017; 171(2):273-285. PMC: 5685180. DOI: 10.1016/j.cell.2017.09.021. View

17.

Stockwell B, Jiang X, Gu W . Emerging Mechanisms and Disease Relevance of Ferroptosis. Trends Cell Biol. 2020; 30(6):478-490. PMC: 7230071. DOI: 10.1016/j.tcb.2020.02.009. View

18.

Ursini F, Maiorino M . Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic Biol Med. 2020; 152:175-185. DOI: 10.1016/j.freeradbiomed.2020.02.027. View

19.

Wang K, Long B, Liu F, Wang J, Liu C, Zhao B . A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 2016; 37(33):2602-11. DOI: 10.1093/eurheartj/ehv713. View

20.

Xia W, Chen H, Xie C, Hou M . Long-noncoding RNA MALAT1 sponges microRNA-92a-3p to inhibit doxorubicin-induced cardiac senescence by targeting ATG4a. Aging (Albany NY). 2020; 12(9):8241-8260. PMC: 7244027. DOI: 10.18632/aging.103136. View