Abstract
Background
Atherosclerosis (AS) was the main cause of serious cardiovascular diseases, which seriously endangered human health. Studies have shown that circRNA plays an important regulatory role in the development of atherosclerosis.
Objective
This study aimed to investigate the molecular mechanism of circular RNA (circRNA) circ_0003204 in the development of atherosclerosis.
Results
The expression levels of circ_0003204 and FOSL2 were significantly increased in atherosclerosis samples and ox-LDL-induced VSMCs, while the expression level of miR-637 was significantly decreased. In ox-LDL-induced VSMCs cells, knockdown of circ_0003204 or miR-637 overexpression could significantly inhibit cell proliferation, migration and invasion. Moreover, miR-637 was the target miRNA of circ_0003204 and directly targeted FOSL2. Overexpression of FOSL2 could rescue the effect of si-circ_0003204 on the phenotypic changes in ox-LDL-induced VSMCs.
Conclusion
In short, circ_0003204 was significantly upregulated in atherosclerotic samples, knockdown of circ_0003204 could inhibit ox-LDL-induced VSMCs injury by miR-637/FOSL2 axis, which might be an effective therapeutic target for AS.
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Data availability
The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
References
Bartal AD, Djaldetti MM, Mandel EM, Lerner MA (1973) Dumb-bell neurinoma of the hypoglossal nerve. J Neurol Neurosurg Psychiatry 36(4):592–595
Bejjani F, Evanno E, Zibara K, Piechaczyk M (1872) Jariel-encontre I (2019) The AP-1 transcriptional complex: Local switch or remote command? Biochim Biophys Acta Rev Cancer 1:11–23
Boren J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ et al (2020) Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the european atherosclerosis society consensus panel. Eur Heart J 41(24):2313–2330
Conti P, haik-Dasthagirisaeb Y (2015) Atherosclerosis: a chronic inflammatory disease mediated by mast cells. Cent Eur J Immunol 40(3):380–386
Dzobo KE, Hanford KML, Kroon J (2021) Vascular metabolism as driver of atherosclerosis: linking endothelial metabolism to inflammation. Immunometabolism 3(3):e210020
Felekkis K, Touvana E, Stefanou C, Deltas C (2010) microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia 14(4):236–240
Gao K, Chen S, Yang X (2021) HOTTIP enhances gemcitabine and cisplatin resistance through sponging miR-637 in cholangiocarcinoma. Front Oncol 11:664916
He L, Man C, Xiang S, Yao L, Wang X, Fan Y (2021) Circular RNAs’ cap-independent translation protein and its roles in carcinomas. Mol Cancer 20(1):119
Kang L, Jia H, Huang B, Lu S, Chen Z, Shen J et al (2021) Identification of differently expressed mrnas in atherosclerosis reveals CDK6 Is regulated by circHIPK3/miR-637 axis and promotes cell growth in human vascular smooth muscle cells. Front Genet 12:596169
Liang Y, Meng K, Qiu R (2021) Circular RNA Circ_0013958 functions as a tumor promoter in ovarian cancer by regulating miR-637/PLXNB2 axis. Front Genet 12:644451
Lin B, Yang J, Song Y, Dang G, Feng J (2021) Exosomes and atherogenesis. Front Cardiovasc Med. 8:738031
Liu H, Ma X, Mao Z, Shen M, Zhu J, Chen F (2020) Circular RNA has_circ_0003204 inhibits oxLDL-induced vascular endothelial cell proliferation and angiogenesis. Cell Signal 70:109595
Lu Y, Thavarajah T, Gu W, Cai J, Xu Q (2018) Impact of miRNA in Atherosclerosis. Arterioscler Thromb Vasc Biol 38(9):e159–e170
Luo H, Li Y, Zhao Y, Chang J, Zhang X, Zou B et al (2021) comprehensive analysis of circRNA expression profiles during cervical carcinogenesis. Front Oncol 11:676609
Qing Y, Li Q, Zhao LY, Shi P, Shan JL, Zhang W (2021) LncRNA-PANDAR regulates the progression of thyroid carcinoma by targeting miR-637/KLK4. J Cancer 12(19):5879–5887
Roy N, Rosas SE (2021) IL-6 Is Associated with progression of coronary artery calcification and mortality in incident dialysis patients. Am J Nephrol 52:745–752
Saner C, Laitinen TT, Nuotio J, Arnup SJ, Harcourt BE, Bekkering S et al (2021) Modest decrease in severity of obesity in adolescence associates with low arterial stiffness. Atherosclerosis 335:23–30
Santos-Rodriguez G, Voineagu I, Weatheritt RJ (2021) Evolutionary dynamics of circular RNAs in primates. Elife 10:e69148
Sun C, He B, Sun M, Lv X, Wang F, Chen J et al (2021a) Yes-associated protein in atherosclerosis and related complications: a potential therapeutic target that requires further exploration. Front Cardiovasc Med 8:704208
Sun X, Deng K, Zang Y, Zhang Z, Zhao B, Fan J et al (2021b) Exploring the regulatory roles of circular RNAs in the pathogenesis of atherosclerosis. Vascul Pharmacol 141:106898
Tabares-Guevara JH, Villa-Pulgarin JA, Hernandez JC (2021) Atherosclerosis: immunopathogenesis and strategies for immunotherapy. Immunotherapy 13:1231–1244
Tafrihi M, Hasheminasab E (2019) MiRNAs: biology, biogenesis, their web-based tools, and databases. Microrna 8(1):4–27
Wan X, Guan S, Hou Y, Qin Y, Zeng H, Yang L et al (2021) FOSL2 promotes VEGF-independent angiogenesis by transcriptionnally activating Wnt5a in breast cancer-associated fibroblasts. Theranostics 11(10):4975–4991
Wang H, Sugimoto K, Lu H, Yang WY, Liu JY, Yang HY et al (2021) HDAC1-mediated deacetylation of HIF1alpha prevents atherosclerosis progression by promoting miR-224-3p-mediated inhibition of FOSL2. Mol Ther Nucleic Acids 23:577–591
Xu F, Shen L, Chen H, Wang R, Zang T, Qian J et al (2021) circDENND1B Participates in the antiatherosclerotic effect of IL-1beta monoclonal antibody in mouse by promoting cholesterol efflux via miR-17-5p/Abca1 axis. Front Cell Dev Biol 9:652032
Yan S, Yue Y, Sun M, Chen Y, Wang X, Qian H (2021) comparative transcriptome analysis reveals relationship among mRNAs, lncRNAs, and circRNAs of slow transit constipation. Biomed Res Int 2021:6672899
Yang N, Dong B, Song Y, Li Y, Kou L, Yang J et al (2020) Downregulation of miR-637 promotes vascular smooth muscle cell proliferation and migration via regulation of insulin-like growth factor-2. Cell Mol Biol Lett 25:30
Yang J, Zhao H, Yuan H, Zhu F, Zhou W (2021) Prevalence and association of mycoplasma infection in the development of coronary artery disease. Braz J Biol 83:e246385
Yu F, Zhang Y, Wang Z, Gong W, Zhang C (2021) Hsa_circ_0030042 regulates abnormal autophagy and protects atherosclerotic plaque stability by targeting eIF4A3. Theranostics 11(11):5404–5417
Zhu G, Chang X, Kang Y, Zhao X, Tang X, Ma C et al (2021) CircRNA: a novel potential strategy to treat thyroid cancer (review). Int J Mol Med 48(5):201
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LW designed and supervised the study, conducted the experiments and drafted the manuscript. XD collected and analyzed the data. LT contributed the methodology. XM operated the software and edited the manuscript.
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Lingjun Wang, Xianglong Meng, Lina Tan Wang, Xiujuan Ding declares that there no conflict of interest.
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All patients and volunteers signed informed consent forms, and the study protocol was approved by the Ethics Committee of Qiqihar NO.1 Hospital.
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13273_2022_316_MOESM2_ESM.jpg
Supplementary Figure S2 The association of circ_0003204 and miR-637 was identified by dual-luciferase reporter assay. ***P<0.001 file2 (JPG 5363 KB)
13273_2022_316_MOESM3_ESM.jpg
Supplementary Figure S3. Knockdown of FOSL2 protected VSMCs from ox-LDL-induced cell injury. (A) RT-qPCR was used to detect the expression of FOSL2 in VSMCs after the treatment of different concentrations of ox-LDL. (B-F) 100 μg/mL of ox-LDL-treated VSMCs were transfected with si-FOSL2 or si-NC. (B) CCK-8 assay was performed to assess the viability of cells. (C) EDU assay was used to detect the proliferative capacity of cells. (D) Wound healing assay was used to assess cell migration. (E and F) Transwell assay was conducted to evaluate cell migration and invasion. **P<0.01, ***P<0.001 file3 (JPG 103 KB)
13273_2022_316_MOESM4_ESM.jpg
Supplementary Figure S1. The effects of ox-LDL treatment on proliferation, migration and invasion of VSMCs. (A) CCK-8 assay was used to determine the effect of ox-LDL on the cell viability of VSMCs. (B and C) The proliferation and migration of VSMCs were detected by EDU assay and wound healing assay. (D and E) Transwell assays were performed to assess the migration and invasion of VSMCs after treatment with different concentrations of ox-LDL for 24 h. (F-H) Western blot assay was performed to detect the protein levels of PCNA and MMP2 in VSMCs treated with different concentrations of ox-LDL for 24 h. *P<0.05, **P<0.01, ***P<0.001 file4 (JPG 311 KB)
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Wang, L., Tan, L., Ding, X. et al. Circ_0003204 downregulation protected vascular smooth muscle cells from ox-LDL-induced injury by acting on miR-637/FOSL2 axis. Mol. Cell. Toxicol. 20, 47–57 (2024). https://doi.org/10.1007/s13273-022-00316-z
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DOI: https://doi.org/10.1007/s13273-022-00316-z