miR-140-5p inhibits the proliferation, migration and invasion of vascular smooth muscle cells by suppressing the expression of NCKAP1
Abstract
Introduction. The occurrence of aortic dissection is related to the proliferation and metastasis of vascular smooth muscle cells. In our present study, we found that the expression of miR-140-5p was inhibited in the wall of abdominal aorta of aortic dissection patients. However, the mechanism of miR-140-5p in the development of aortic dissection is unclear.
Material and methods. We detected the expression of miR-140-5p and NCK Associated Protein 1 (NCKAP1) in blood vessel of aortic dissection patients and normal people by PCR. Next, we established the miR-140-5p overexpression and miR-140-5p inhibition vascular smooth muscle cells (CRL-1999 cells). The BrdU assays, wound healing assays and transwell assays were performed to detect the proliferation and invasion ability of these cells. Finally, luciferase reporter assay was performed to detect the relationship between miR-140-5p and NCKAP1.
Results. The expression of miR-140-5p was suppressed in blood vessel of aortic dissection patients, and the levels of NCKAP1 in those tissues were upregulated. Overexpression of miR-140-5p inhibited the proliferation, migration and invasion of vascular smooth muscle cells. miR-140-5p targeted and suppressed the expression of NCKAP1.
Conclusions. miR-140-5p repressed the proliferation, migration and invasion of vascular smooth muscle cells by targeting and inhibiting the expression of NCKAP1. Furthermore, the results of our study suggest new strategies and targets for the clinical treatment of arterial dissection.
Keywords: aortic dissectionmiR-140-5pNCKAP1vascular smooth muscle cellsproliferationinvasion
References
- Golledge J, Eagle K. Acute aortic dissection. The Lancet. 2008; 372(9632): 55–66.
- Parthenakis F, Koutalas E, Patrianakos A, et al. Diagnosing acute aortic syndromes: The role of specific biochemical markers. Int J Cardiol. 2010; 145(1): 3–8.
- Pagni S, Ganzel B, Trivedi J, et al. Early and Midterm Outcomes Following Surgery for Acute Type A Aortic Dissection. J Card Surg. 2013; 28(5): 543–549.
- Mészáros I, Mórocz J, Szlávi J, et al. Epidemiology and Clinicopathology of Aortic Dissection. Chest. 2000; 117(5): 1271–1278.
- X. Wei, Y. Sun, Y. Wu, J. Zhu, B. Gao, H. Yan, Z. Zhao, J. Zhou, Z. Jing, Downregulation of Talin-1 expression associates with increased proliferation and migration of vascular smooth muscle cells in aortic dissection, BMC Cardiovasc Disord. 2017; 17: 162.
- Hao H, Gabbiani G, Bochaton-Piallat ML. Arterial Smooth Muscle Cell Heterogeneity. Arterioscler Thromb Vasc Biol. 2003; 23(9): 1510–1520.
- Salabei J, Hill B. Implications of autophagy for vascular smooth muscle cell function and plasticity. Free Radic Biol Med. 2013; 65: 693–703.
- Y.Y. Jin, J.F. Wang, X.J. Wang, L. et al. Roles of non-coding RNA in pancreatic islet development and functioning. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2014; 36: 691–696.
- A. Schwarzer, S. Emmrich, F. Schmidt, et al. Klusmann, The non-coding RNA landscape of human hematopoiesis and leukemia, Nat Commun. 2017; 8 (1): 218.
- Wang Y, Dong CQ, Peng GY, et al. MicroRNA-134-5p Regulates Media Degeneration through Inhibiting VSMC Phenotypic Switch and Migration in Thoracic Aortic Dissection. Molecular Therapy - Nucleic Acids. 2019; 16: 284–294.
- Yu Y, Shi E, Gu T, et al. Overexpression of microRNA-30a contributes to the development of aortic dissection by targeting lysyl oxidase. J Thorac Cardiovasc Surg. 2017; 154(6): 1862–1869.
- World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects, J Am Coll Dent. 2014; 81: 14–18.
- Walton T, Li G, McCulloch T, et al. Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissue. The Prostate. 2009; 69(8): 810–819.
- Takeda N, Komuro I. Genetic basis of hereditary thoracic aortic aneurysms and dissections. J Cardiol. 2019; 74(2): 136–143.
- Martino ADe, Morganti R, Falcetta G, et al. Acute aortic dissection and pregnancy: Review and meta‐analysis of incidence, presentation, and pathologic substrates. J Card Surg. 2019; 34(12): 1591–1597.
- Barbour J, Spinale F, Ikonomidis J. Proteinase Systems and Thoracic Aortic Aneurysm Progression. J Surg Res. 2007; 139(2): 292–307.
- R. Li, X. Yi, X. Wei, et al. EZH2 inhibits autophagic cell death of aortic vascular smooth muscle cells to affect aortic dissection. Cell Death Dis. 2018; 9: 180.
- Choi M, Lee I, Kim G, et al. Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II. Nature. 2005; 435(7040): 347–353.
- Hopkins P. Molecular Biology of Atherosclerosis. Physiol Rev. 2013; 93(3): 1317–1542.
- L. Xue, S. Luo, H. Ding, et al. Upregulation of miR-146a-5p is associated with increased proliferation and migration of vascular smooth muscle cells in aortic dissection, J Clin Lab Anal. 2019; 33: e22843.
- Clément M, Chappell J, Raffort J, et al. Vascular Smooth Muscle Cell Plasticity and Autophagy in Dissecting Aortic Aneurysms. Arterioscler Thromb Vasc Biol. 2019; 39(6): 1149–1159.
- Rothman A, Arnold N, Pickworth J, et al. MicroRNA-140-5p and SMURF1 regulate pulmonary arterial hypertension. J Clin Invest. 2016; 126(7): 2495–2508.
- Zhang Y, Xu J. miR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 and promoting SOD2 expression. Biochem Biophys Res Commun. 2016; 473(1): 342–348.
- Loginov VI, Rykov SV, Fridman MV, et al. Methylation of miRNA genes and oncogenesis. Biochemistry (Moscow). 2015; 80(2): 145–162.
- Nakao S, Platek A, Hirano S, et al. Contact-dependent promotion of cell migration by the OL-protocadherin–Nap1 interaction. J Cell Biol. 2008; 182(2): 395–410.
- Lomakina M, Lallemand F, Vacher S, et al. Arpin downregulation in breast cancer is associated with poor prognosis. Br J Cancer. 2016; 114(5): 545–553.