Skip to main content

Advertisement

SpringerLink
Log in

Circ_0004872 deficiency attenuates ox-LDL-induced vascular smooth muscle cell dysfunction by miR-424-5p-dependent regulation of FRS2

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Atherosclerosis (AS) is a pivotal pathological basis of cardiovascular and cerebrovascular diseases, and circular RNAs (circRNAs) has been disclosed to exert a vital part in the progression of AS. However, the functions of circ_0004872 in the progression of AS is indistinct. In this context, we aimed to elucidate the role of circ_0004872 and the potential mechanism in AS. The level of circ_0004872, miR-424-5p and fibroblast growth factor receptor substrate 2 (FRS2) was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was monitored by Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine (EDU) assays. The invasion and migration capabilities of VSMCs were tested by transwell assays and wound-healing assay, respectively. Western blot was adopted to check the protein levels of CyclinD1, Vimentin and FRS2. Dual-luciferase reporter and RNA immunoprecipitation assay were executed to manifest the interaction between miR-424-5p and circ_0004872 or FRS2. The level of circ_0004872 was increased in the serum samples of AS patients and ox-LDL-exposed VSMCs. Ox-LDL exposure triggered cell proliferation, invasion and migration ability of VSMCs. depletion of circ_0004872 partly weakened ox-LDL-mediated effects in VSMCs. Mechanistically, circ_0004872 functioned as a sponge of miR-424-5p, and miR-424-5p inhibition partly alleviated circ_0004872 deficiency-mediated influences in VSMCs. Additionally, miR-424-5p interacted with FRS2, and miR-424-5p constrained dysfunction in ox-LDL-stimulated VSMCs via reducing FRS2 level. Notably, circ_0004872 functioned as a sponge of miR-424-5p to elevate FRS2 expression. Circ_0004872 accelerated ox-LDL-induced damage via mediating miR-424-5p/FRS2 axis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Glaucylara Reis G, Peter L (2018) Atherosclerosis and inflammation: overview and updates. Clin Sci 132(12):1243–1252

    Article  Google Scholar 

  2. Moriya J (2018) Critical roles of inflammation in atherosclerosis. J Cardiol 73(1):22–27

    Article  PubMed  Google Scholar 

  3. Basatemur GL, Jrgensen HF, Clarke M, Bennett MR, Mallat Z (2019) Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol 16(12):1

    Article  Google Scholar 

  4. Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM (2018) Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness. Cardiovasc Res 114(4):590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang Y, Liu J, Ma J, Sun T, Ming L (2019) Exosomal circRNAs: biogenesis, effect and application in human diseases. Mol Cancer 18(1):116

    Article  PubMed  PubMed Central  Google Scholar 

  6. Verduci L, Tarcitano E, Strano S, Yarden Y, Blandino G (2021) CircRNAs: role in human diseases and potential use as biomarkers. Cell Death Dis 12(5):468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Qiu Y, Pu C, Li Y, Qi B (2020) Construction of a circRNA-miRNA-mRNA network based on competitive endogenous RNA reveals the function of circRNAs in osteosarcoma. Cancer Cell Int 20:48

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cao Q, Guo Z, Du S, Ling H, Song C (2020) Circular RNAs in the pathogenesis of atherosclerosis. Life Sci 255:117837

    Article  CAS  PubMed  Google Scholar 

  9. 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. Mol Cell Biochem 476(11):3899–3910

    Article  CAS  PubMed  Google Scholar 

  10. Ding P, Ding Y, Tian Y, Lei X (2020) Circular RNA circ_0010283 regulates the viability and migration of oxidized low-density lipoprotein-induced vascular smooth muscle cells via an miR-370-3p/HMGB1 axis in atherosclerosis. Int J Mol Med 46(4):1399–1408

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Peng W, Li T, Pi S, Huang L, Liu Y (2020) Suppression of circular RNA circDHCR24 alleviates aortic smooth muscle cell proliferation and migration by targeting miR-149-5p/MMP9 axis. Biochem Biophys Res Commun 529(3):753–759

    Article  CAS  PubMed  Google Scholar 

  12. 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. Vasc Pharmacol 140:106842

    Article  CAS  Google Scholar 

  13. Liang Y, Song X, Li Y, Chen B, Zhao W, Wang L et al (2020) LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis. Mol Cancer 19(1):85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wolf D, Ley K (2019) Immunity and inflammation in atherosclerosis. Herz 44(2):107–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Grootaert M, Bennett MR (2021) Vascular smooth muscle cells in atherosclerosis: time for a reassessment. Cardiovasc Res 11(11):2326–2339

    Article  Google Scholar 

  16. Chen Z, Pan X, Sheng Z et al (2019) Baicalin suppresses the proliferation and migration of Ox-LDL-VSMCs in atherosclerosis through upregulating miR-126-5p. Biol Pharm Bull 42(9):1517–1523

    Article  CAS  PubMed  Google Scholar 

  17. Wang H, Hu H, Ma J, Jiang Y, Cheng R (2021) lncRNA ZFAS1 promotes the oxLDL induced proliferation, invasion and migration of vascular smooth muscle cells. Exp Ther Med 22(2):835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang F, Zhang R, Zhang X, Wu Y, Li X, Zhang S et al (2018) Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits. Aging 10(9):2266–2283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rong D, Sun H, Li Z, Liu S, Cao H (2015) An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 8(42):73271–73281

    Article  Google Scholar 

  20. Ma C, Wang X, Yang F, Zang Y, Liu J, Wang X et al (2020) Circular RNA hsa_circ_0004872 inhibits gastric cancer progression via the miR-224/Smad4/ADAR1 successive regulatory circuit. Mol Cancer 19(1):157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Panda AC (2018) Circular RNAs act as miRNA sponges. Adv Exp Med Biol 1084:67–79

    Article  Google Scholar 

  22. Li W, Li G, Liu Z, Chen Z, Pu R (2021) LncRNA LINC00355 promotes EMT and metastasis of bladder cancer cells through the miR-424-5p/HMGA2 axis. Neoplasma 68(6):1225–1235

    Article  CAS  PubMed  Google Scholar 

  23. Ye Z, He Q, Wang Q, Lin Y, Cen K, Chen X (2021) LINC00922 promotes the proliferation, migration, invasion and EMT process of liver cancer cells by regulating miR-424-5p/ARK5. Mol Cell Biochem 476(10):3757–3769

    Article  CAS  PubMed  Google Scholar 

  24. Ma L, Liang L, Zhou D, Wang S (2021) Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4. Neoplasma 68(1):165–173

    Article  CAS  PubMed  Google Scholar 

  25. Yue X, Wang Z (2020) Long intergenic non-coding RNA LINC00922 aggravates the malignant phenotype of breast cancer by regulating the microRNA-424-5p/BDNF axis. Cancer Manag Res 12:7539–7552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yu H, Zhao L, Zhao Y, Fei J, Zhang W (2020) Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424-5p/IGF2 axis. Vasc Pharmacol 135:106782

    Article  CAS  Google Scholar 

  27. Li C, Zhang M, Dai Y, Xu Z (2020) MicroRNA-424-5p regulates aortic smooth muscle cell function in atherosclerosis by blocking APOC3-mediated nuclear factor-κB signalling pathway. Exp Physiol 105(6):1035–1049

    Article  CAS  PubMed  Google Scholar 

  28. Lu Y, Thavarajah T, Gu W et al (2018) Impact of miRNA in atherosclerosis. Arterioscler Thromb Vasc Biol 38(9):e159–e170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Huang T, Zhao H, Zhang X, Gao X, Peng W, Zhou Y et al (2020) LncRNA ANRIL regulates cell proliferation and migration via sponging miR-339-5p and regulating FRS2 expression in atherosclerosis. Eur Rev Med Pharmacol Sci 24(4):1956–1969

    CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Henan Province Young and Middle-aged Health Innovation Outstanding Young Talents Training Project (No. YXKC2021051); Henan Province High-Level Talent Internationalization Training Funding Project [Yuke(2022)-3] and Henan Province Medical Science and Technology Joint Construction Project (No. LHGJ20210110).

Author information

Author notes

  1. Peng Qian and Xuanchao Cao have contributed equally to this paper.

Authors and Affiliations

  1. Department of Geriatric Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, 450003, China

    Peng Qian, Xuanchao Cao, Qian Zhang, Meihua Gao & Xin Liu

  2. Heart Center of Henan Provincial People’s Hospital, Fuwai Central China Cardiovascular Hospital, Fuwai Central China Hospital of Zhengzhou University, No. 1 Fuwai Street, Zhengdong New District, Zhengzhou, 451464, China

    Lijie Yan

Authors
  1. Peng Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuanchao Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meihua Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lijie Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LY designed and supervised the study. PQ and XC performed experiments and wrote the manuscript. QZ and MC collected data and analyzed data. XL prepared the figures and edited the manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Lijie Yan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All participators have been signed written informed consent. The protocols were approved by the Ethics Committee of Henan Provincial People’s Hospital and was performed in accordance with the Declaration of Helsinki.

Informed consent

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

11010_2024_4929_MOESM1_ESM.tif

Supplementary file1 (TIF 128 kb) Supplementary Fig. 1 interference of circ_0004872 effectively rescued ox-LDL-evoked increase of MMP2 and MMP9. MMP2 and MMP9 levels were monitored by western blot analysis in VSMCs. n = 3. Two-way ANOVA followed by Tukey's test. **P < 0.01, ***P < 0.001, ****P < 0.0001

11010_2024_4929_MOESM2_ESM.tif

Supplementary file2 (TIF 73 kb) Supplementary Fig. 2 Circ_0004872 was significantly highly expressed in AS patients. The expression of multiple circRNAs was detected by qRT-PCR. n = 3. Two-way ANOVA followed by Tukey's test. ****P < 0.0001

11010_2024_4929_MOESM3_ESM.tif

Supplementary file3 (TIF 61 kb) Supplementary Fig. 3 Overexpression of miR-424-5p could significantly inhibit the expression of FRS2. The level of multiple mRNAs were monitored by qRT-PCR. n = 3. Two-way ANOVA followed by Tukey's test. *P < 0.05, ****P < 0.0001

11010_2024_4929_MOESM4_ESM.tif

Supplementary file4 (TIF 1158 kb) Supplementary Fig. 4 Overexpression of circ_0004872 accelerated proliferation and invasion of ox-LDL-treated VSMC. A Circ_0004872 expression was assessed in VSMC transfected with circ_0004872 or pCD5-ciR by qRT-PCR. B, C CCK8 and EdU assays were used to measure the proliferation ability of VSMCs. D Invasion capabilities of VSMC were explored by transwell assay. n = 3. A–D One-way ANOVA followed by Tukey's test. **P < 0.01, ***P < 0.001 or ****P < 0.0001

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qian, P., Cao, X., Zhang, Q. et al. Circ_0004872 deficiency attenuates ox-LDL-induced vascular smooth muscle cell dysfunction by miR-424-5p-dependent regulation of FRS2. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04929-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11010-024-04929-x

Keywords

Search

Navigation