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Published in: Cardiovascular Toxicology 2/2024

20-02-2024 | Arterial Occlusive Disease | Research

Hsa_circ_0032389 Enhances Proliferation and Migration in PDGF-BB-Induced Human Aortic Vascular Smooth Muscle Cells

Authors: Haiyun Qian, Shengwei Ma, Qian Zhou, Chengang Lei

Published in: Cardiovascular Toxicology | Issue 2/2024

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Abstract

Circular RNA (circRNAs) has been confirmed to participate in atherosclerosis (AS) progression. However, the role and mechanism of hsa_circ_0032389 in AS process still need to be further revealed. This study evaluates the role and mechanism of hsa_circ_0032389 in AS process. Platelet-derived growth factor-BB (PDGF-BB) was used to induce human aortic vascular smooth muscle cells (HA-VSMCs). The expression levels of hsa_circ_0032389, microRNA (miR)-513a-5p, and fibroblast growth factor receptor substrate 2 (FRS2) were examined by quantitative real-time PCR. Cell proliferation and migration were analyzed using cell counting kit 8 assay, flow cytometry, EdU assay, transwell assay, and wound healing assay. Protein expression was assessed using western blot analysis. Dual-luciferase reporter and RIP assays were used to confirm RNA interaction. Hsa_circ_0032389 was overexpressed in PDGF-BB-induced HA-VSMCs, and its downregulation inhibited HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate under PDGF-BB treatment. The luciferase activity of hsa_circ_0032389wt could be reduced by miR-513a-5p mimic, and both hsa_circ_0032389 and miR-513a-5p were enriched in anti-Ago2, confirming that miR-513a-5p could be sponged by hsa_circ_0032389. MiR-513a-5p inhibitor reversed the effect of hsa_circ_0032389 knockdown on PDGF-BB-induced HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate. Moreover, the luciferase activity of FRS2wt was reduced by miR-513a-5p mimic, and both FRS2 and miR-513a-5p were enriched in anti-Ago2, verifying that FRS2 was targeted by miR-513a-5p. MiR-513a-5p suppressed PDGF-BB-induced HA-VSMC viability, cell cycle, EdU positive cell rate, migratory cell number, and wound closure rate by targeting FRS2. Our results indicated that hsa_circ_0032389 enhanced PDGF-BB-induced HA-VSMC proliferation and migration via regulating miR-513a-5p/FRS2 axis.
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Literature
1.
go back to reference Alkan, A. H, & Akgul, B. (2022). Endogenous miRNA sponges. Methods in Molecular Biology, 2257, 91–104.CrossRefPubMed Alkan, A. H, & Akgul, B. (2022). Endogenous miRNA sponges. Methods in Molecular Biology, 2257, 91–104.CrossRefPubMed
2.
go back to reference Fan, J, & Watanabe, T. (2022). Atherosclerosis: Known and unknown. Pathology International, 72(3), 151–160.CrossRefPubMed Fan, J, & Watanabe, T. (2022). Atherosclerosis: Known and unknown. Pathology International, 72(3), 151–160.CrossRefPubMed
3.
go back to reference Fan, K, Ruan, X, Wang, L, Lu, W, Shi, Q, & Xu, Y. (2021). Circ_0004872 promotes platelet-derived growth factor-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs via miR-513a-5p/TXNIP axis. Vascular Pharmacology, 140, 106842.CrossRefPubMed Fan, K, Ruan, X, Wang, L, Lu, W, Shi, Q, & Xu, Y. (2021). Circ_0004872 promotes platelet-derived growth factor-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs via miR-513a-5p/TXNIP axis. Vascular Pharmacology, 140, 106842.CrossRefPubMed
4.
go back to reference Formichi, C, Nigi, L, Grieco, G. E, Maccora, C, Fignani, D, Brusco, N, Licata, G, Sebastiani, G, & Dotta, F. (2021). Non-coding RNAs: novel players in insulin resistance and related diseases. International Journal of Molecular Sciences, 22, 14.CrossRef Formichi, C, Nigi, L, Grieco, G. E, Maccora, C, Fignani, D, Brusco, N, Licata, G, Sebastiani, G, & Dotta, F. (2021). Non-coding RNAs: novel players in insulin resistance and related diseases. International Journal of Molecular Sciences, 22, 14.CrossRef
5.
go back to reference Fu, X, Niu, T, Yang, T, & Li, X. (2021). CircMAPK1 promotes the proliferation and migration of vascular smooth muscle cells through miR-22-3p/ methyl-CpG binding protein 2 axis. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD, 31(7), 2189–2198.CrossRefPubMed Fu, X, Niu, T, Yang, T, & Li, X. (2021). CircMAPK1 promotes the proliferation and migration of vascular smooth muscle cells through miR-22-3p/ methyl-CpG binding protein 2 axis. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD, 31(7), 2189–2198.CrossRefPubMed
6.
go back to reference Grootaert, M. O. J, & Bennett, M. R. (2021). Vascular smooth muscle cells in atherosclerosis: Time for a re-assessment. Cardiovascular Research, 117(11), 2326–2339.CrossRefPubMedPubMedCentral Grootaert, M. O. J, & Bennett, M. R. (2021). Vascular smooth muscle cells in atherosclerosis: Time for a re-assessment. Cardiovascular Research, 117(11), 2326–2339.CrossRefPubMedPubMedCentral
7.
go back to reference Huang, X, Zhao, Y, Zhou, H, & Li, Y. (2022). Circular RNAs in atherosclerosis. Clinica Chimica Acta: International Journal of Clinical Chemistry, 531, 71–80.CrossRefPubMed Huang, X, Zhao, Y, Zhou, H, & Li, Y. (2022). Circular RNAs in atherosclerosis. Clinica Chimica Acta: International Journal of Clinical Chemistry, 531, 71–80.CrossRefPubMed
8.
go back to reference Jebari-Benslaiman, S, Galicia-Garcia, U, Larrea-Sebal, A, Olaetxea, J. R, Alloza, I, Vandenbroeck, K, Benito-Vicente, A, & Martin, C. (2022). Pathophysiology of atherosclerosis. International Journal of Molecular Sciences, 23, 6.CrossRef Jebari-Benslaiman, S, Galicia-Garcia, U, Larrea-Sebal, A, Olaetxea, J. R, Alloza, I, Vandenbroeck, K, Benito-Vicente, A, & Martin, C. (2022). Pathophysiology of atherosclerosis. International Journal of Molecular Sciences, 23, 6.CrossRef
9.
go back to reference Jo, J. H, Park, H. S, Lee, D. H, Han, J. H, Heo, K. S, & Myung, C. S. (2021). Rosuvastatin inhibits the apoptosis of platelet-derived growth factor-stimulated vascular smooth muscle cells by inhibiting p38 via autophagy. The Journal of Pharmacology and Experimental Therapeutics, 378(1), 10–19.CrossRefPubMed Jo, J. H, Park, H. S, Lee, D. H, Han, J. H, Heo, K. S, & Myung, C. S. (2021). Rosuvastatin inhibits the apoptosis of platelet-derived growth factor-stimulated vascular smooth muscle cells by inhibiting p38 via autophagy. The Journal of Pharmacology and Experimental Therapeutics, 378(1), 10–19.CrossRefPubMed
10.
go back to reference Liu, Y, Sun, J, Qi, P, & Liu, Y. (2021). Long non-coding RNA titin-antisense RNA1 contributes to growth and metastasis of cholangiocarcinoma by suppressing microRNA-513a-5p to upregulate stratifin. Bioengineered, 12(2), 12611–12624.CrossRefPubMedPubMedCentral Liu, Y, Sun, J, Qi, P, & Liu, Y. (2021). Long non-coding RNA titin-antisense RNA1 contributes to growth and metastasis of cholangiocarcinoma by suppressing microRNA-513a-5p to upregulate stratifin. Bioengineered, 12(2), 12611–12624.CrossRefPubMedPubMedCentral
11.
go back to reference Liu, Y. X, Yuan, P. Z, Wu, J. H, & Hu, B. (2021). Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis. Journal of Molecular Medicine, 99(11), 1511–1526.CrossRefPubMed Liu, Y. X, Yuan, P. Z, Wu, J. H, & Hu, B. (2021). Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis. Journal of Molecular Medicine, 99(11), 1511–1526.CrossRefPubMed
12.
go back to reference Ma, W, Wei, D, Li, X, Shan, L, Fan, H, Jin, H, Song, B, & Zhang, B. (2022). CircPCNX promotes PDGF-BB-induced proliferation and migration of human aortic vascular smooth muscle cells through regulating miR-1278/DNMT1 axis. Cardiovascular Drugs and Therapy, 37, 877.CrossRefPubMed Ma, W, Wei, D, Li, X, Shan, L, Fan, H, Jin, H, Song, B, & Zhang, B. (2022). CircPCNX promotes PDGF-BB-induced proliferation and migration of human aortic vascular smooth muscle cells through regulating miR-1278/DNMT1 axis. Cardiovascular Drugs and Therapy, 37, 877.CrossRefPubMed
13.
go back to reference Mao, Q, & Zou, H. (2021). Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia. Reproductive Biology, 21(4), 100571.CrossRefPubMed Mao, Q, & Zou, H. (2021). Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia. Reproductive Biology, 21(4), 100571.CrossRefPubMed
14.
go back to reference Maruhashi, T, Kajikawa, M, Kishimoto, S, Takaeko, Y, Yamaji, T, Harada, T, Hashimoto, Y, Han, Y, Yusoff, F. M, Nakano, Y, et al. (2021). Upstroke time as a marker of atherosclerosis in patients with diabetes mellitus who have a normal ankle-brachial index. Journal of Diabetes and Its Complications, 35(11), 108044.CrossRefPubMed Maruhashi, T, Kajikawa, M, Kishimoto, S, Takaeko, Y, Yamaji, T, Harada, T, Hashimoto, Y, Han, Y, Yusoff, F. M, Nakano, Y, et al. (2021). Upstroke time as a marker of atherosclerosis in patients with diabetes mellitus who have a normal ankle-brachial index. Journal of Diabetes and Its Complications, 35(11), 108044.CrossRefPubMed
15.
go back to reference Miao, X, Tian, Y, Wu, L, Zhao, H, Liu, J, Gao, F, Zhang, W, Liu, Q, Guo, H, Yang, L, et al. (2022). CircRTN4 aggravates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis. Laboratory Investigation: A Journal of Technical Methods and Pathology, 102, 966.CrossRefPubMed Miao, X, Tian, Y, Wu, L, Zhao, H, Liu, J, Gao, F, Zhang, W, Liu, Q, Guo, H, Yang, L, et al. (2022). CircRTN4 aggravates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis. Laboratory Investigation: A Journal of Technical Methods and Pathology, 102, 966.CrossRefPubMed
16.
go back to reference Min, X, Liu, D. L, & Xiong, X. D. (2021). Circular RNAs as competing endogenous RNAs in cardiovascular and cerebrovascular diseases: Molecular mechanisms and clinical implications. Frontiers in Cardiovascular Medicine, 8, 682357.CrossRefPubMedPubMedCentral Min, X, Liu, D. L, & Xiong, X. D. (2021). Circular RNAs as competing endogenous RNAs in cardiovascular and cerebrovascular diseases: Molecular mechanisms and clinical implications. Frontiers in Cardiovascular Medicine, 8, 682357.CrossRefPubMedPubMedCentral
17.
go back to reference Ono, K, Horie, T, Baba, O, Kimura, M, Tsuji, S, Rodriguez, R. R, Miyagawa, S, & Kimura, T. (2021). Functional non-coding RNAs in vascular diseases. The FEBS Journal, 288(22), 6315–6330.CrossRefPubMedPubMedCentral Ono, K, Horie, T, Baba, O, Kimura, M, Tsuji, S, Rodriguez, R. R, Miyagawa, S, & Kimura, T. (2021). Functional non-coding RNAs in vascular diseases. The FEBS Journal, 288(22), 6315–6330.CrossRefPubMedPubMedCentral
18.
go back to reference Sun, C, Li, J, Li, Y, Li, L, & Huang, G. (2021). Circular RNA circUBR4 regulates ox-LDL-induced proliferation and migration of vascular smooth muscle cells through miR-185-5p/FRS2 axis. Molecular and Cellular Biochemistry, 476(11), 3899–3910.CrossRefPubMed Sun, C, Li, J, Li, Y, Li, L, & Huang, G. (2021). Circular RNA circUBR4 regulates ox-LDL-induced proliferation and migration of vascular smooth muscle cells through miR-185-5p/FRS2 axis. Molecular and Cellular Biochemistry, 476(11), 3899–3910.CrossRefPubMed
19.
go back to reference Sun, X, Deng, K, Zang, Y, Zhang, Z, Zhao, B, Fan, J, & Huang, L. (2021). Exploring the regulatory roles of circular RNAs in the pathogenesis of atherosclerosis. Vascular Pharmacology, 141, 106898.CrossRefPubMed Sun, X, Deng, K, Zang, Y, Zhang, Z, Zhao, B, Fan, J, & Huang, L. (2021). Exploring the regulatory roles of circular RNAs in the pathogenesis of atherosclerosis. Vascular Pharmacology, 141, 106898.CrossRefPubMed
20.
go back to reference Sung, L. C, Chang, C. C, Lin, C. S, Yeh, C. C, Cherng, Y. G, Chen, T. L, & Liao, C. C. (2021). Risk of acute atherosclerotic cardiovascular disease in patients with acute and chronic pancreatitis. Scientific Reports, 11(1), 20907.ADSCrossRefPubMedPubMedCentral Sung, L. C, Chang, C. C, Lin, C. S, Yeh, C. C, Cherng, Y. G, Chen, T. L, & Liao, C. C. (2021). Risk of acute atherosclerotic cardiovascular disease in patients with acute and chronic pancreatitis. Scientific Reports, 11(1), 20907.ADSCrossRefPubMedPubMedCentral
21.
go back to reference Turner, N, & Grose, R. (2010). Fibroblast growth factor signalling: From development to cancer. Nature Reviews Cancer, 10(2), 116–129.CrossRefPubMed Turner, N, & Grose, R. (2010). Fibroblast growth factor signalling: From development to cancer. Nature Reviews Cancer, 10(2), 116–129.CrossRefPubMed
22.
go back to reference Wu, Q, Chen, J, Tan, Z, Wang, D, Zhou, J, Li, D, & Cen, Y. (2021). Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) regulates fibroblast growth factor receptor substrate 2 (FRS2) by targeting microRNA (miR)-29-3p in hypertrophic scar fibroblasts. Bioengineered, 12(1), 5210–5219.CrossRefPubMedPubMedCentral Wu, Q, Chen, J, Tan, Z, Wang, D, Zhou, J, Li, D, & Cen, Y. (2021). Long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) regulates fibroblast growth factor receptor substrate 2 (FRS2) by targeting microRNA (miR)-29-3p in hypertrophic scar fibroblasts. Bioengineered, 12(1), 5210–5219.CrossRefPubMedPubMedCentral
23.
go back to reference Xiang, Y, Li, L, Xia, S, Lv, J, & Li, X. (2021). Cullin3 (CUL3) suppresses proliferation, migration and phenotypic transformation of PDGF-BB-stimulated vascular smooth muscle cells and mitigates inflammatory response by repressing Hedgehog signaling pathway. Bioengineered, 12(2), 9463–9472.CrossRefPubMedPubMedCentral Xiang, Y, Li, L, Xia, S, Lv, J, & Li, X. (2021). Cullin3 (CUL3) suppresses proliferation, migration and phenotypic transformation of PDGF-BB-stimulated vascular smooth muscle cells and mitigates inflammatory response by repressing Hedgehog signaling pathway. Bioengineered, 12(2), 9463–9472.CrossRefPubMedPubMedCentral
24.
go back to reference Yan, Y, Li, T, Li, Z, He, M, Wang, D, Xu, Y, Yang, X, Bai, Y, Lao, Y, Zhang, Z, et al. (2021). Metformin suppresses the progress of diabetes-accelerated atherosclerosis by inhibition of vascular smooth muscle cell migration through AMPK-Pdlim5 pathway. Frontiers in Cardiovascular Medicine, 8, 690627.CrossRefPubMedPubMedCentral Yan, Y, Li, T, Li, Z, He, M, Wang, D, Xu, Y, Yang, X, Bai, Y, Lao, Y, Zhang, Z, et al. (2021). Metformin suppresses the progress of diabetes-accelerated atherosclerosis by inhibition of vascular smooth muscle cell migration through AMPK-Pdlim5 pathway. Frontiers in Cardiovascular Medicine, 8, 690627.CrossRefPubMedPubMedCentral
25.
go back to reference Yang, Y, Mao, W, Wang, L, Lu, L, & Pang, Y. (2022). Circular RNA circLMF1 regulates PDGF-BB-induced proliferation and migration of human aortic smooth muscle cells by regulating the miR-125a-3p/VEGFA or FGF1 axis. Clinical Hemorheology and Microcirculation, 80(2), 167–183.CrossRefPubMed Yang, Y, Mao, W, Wang, L, Lu, L, & Pang, Y. (2022). Circular RNA circLMF1 regulates PDGF-BB-induced proliferation and migration of human aortic smooth muscle cells by regulating the miR-125a-3p/VEGFA or FGF1 axis. Clinical Hemorheology and Microcirculation, 80(2), 167–183.CrossRefPubMed
26.
go back to reference Zhao, L, Wang, B, Sun, L, Sun, B, & Li, Y. (2021). Association of miR-192-5p with atherosclerosis and its effect on proliferation and migration of vascular smooth muscle cells. Molecular Biotechnology, 63(12), 1244–1251.CrossRefPubMed Zhao, L, Wang, B, Sun, L, Sun, B, & Li, Y. (2021). Association of miR-192-5p with atherosclerosis and its effect on proliferation and migration of vascular smooth muscle cells. Molecular Biotechnology, 63(12), 1244–1251.CrossRefPubMed
27.
go back to reference Zheng, X, Liu, J, Gong, X, Zhang, X, & Ma, S. (2021). Circ_0002984 enhances growth, invasion, and migration in pdgf-bb-induced vascular smooth muscle cells through miR-379-5p/FRS2 Axis. Journal of Cardiovascular Pharmacology, 78(6), 875–884.CrossRefPubMed Zheng, X, Liu, J, Gong, X, Zhang, X, & Ma, S. (2021). Circ_0002984 enhances growth, invasion, and migration in pdgf-bb-induced vascular smooth muscle cells through miR-379-5p/FRS2 Axis. Journal of Cardiovascular Pharmacology, 78(6), 875–884.CrossRefPubMed
Metadata
Title
Hsa_circ_0032389 Enhances Proliferation and Migration in PDGF-BB-Induced Human Aortic Vascular Smooth Muscle Cells
Authors
Haiyun Qian
Shengwei Ma
Qian Zhou
Chengang Lei
Publication date
20-02-2024
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 2/2024
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-024-09833-w

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