Study of circTRRAP knockdown in acute myocardial infarction by regulating miR-323-3p/SMAD2 axis

Xiong Yan, Tang Yijia

PDF(5434 KB)
PDF(5434 KB)
Journal of Chongqing Medical University ›› 2025, Vol. 50 ›› Issue (04) : 547-556. DOI: 10.13406/j.cnki.cyxb.003788
Clinical research

Study of circTRRAP knockdown in acute myocardial infarction by regulating miR-323-3p/SMAD2 axis

Author information +
History +

Abstract

Objective To investigate the specific role of circTRRAP in acute myocardial infarction(AMI). Methods The method of hypoxia for 24 hours was used to induce the model of myocardial infarction,and the dual-luciferase reporter assay was used to investigate the interaction between circTRRAP,SMAD2,and miR-323-3p. After knockdown and overexpression of miR-323-3p and overexpression of SMAD2 through transfection with si-circTRRAP,the expression levels of proinflammatory cytokines [interkeukin-6(IL-6) and tumor necrosis factor-α(TNF-α)],oxidative stress markers [malondialdehyde(MDA) and superoxide dismutase(SOD)],and apoptotic factors[Bcl-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2),and cleaved caspase-3]were measured to investigate the role of circTRRAP,SMAD2,and miR-323-3p in myocardial infarction. Results In the model of myocardial infarction injury,the levels of circTRRAP and SMAD2 were significantly increased by more than 50%,whereas there was a significant reduction in the expression of miR-323-3p. The downregulation of circTRRAP led to a reduction in SMAD2 expression by promoting miR-323-3p expression. SMAD2 was negatively correlated with miR-323-3p,but it was positively correlated with the expression of circTRRAP. The downregulation of circTRRAP or SMAD2 or the upregulation of miR-323-3p could increase cell viability and reduce the apoptosis rate of cardiomyocytes. Conclusion Downregulation of circTRRAP can inhibit inflammation and alleviate AMI via the miR-323-3p/SMAD2 axis.

Key words

circular RNA / gene regulation / cell apoptosis / myocardial infarction

Cite this article

Download Citations
Xiong Yan , Tang Yijia. Study of circTRRAP knockdown in acute myocardial infarction by regulating miR-323-3p/SMAD2 axis. Journal of Chongqing Medical University. 2025, 50(04): 547-556 https://doi.org/10.13406/j.cnki.cyxb.003788

References

1
韦亚忠,薛晓梅,何 斌. 活性氧介导心肌缺血再灌注损伤的研究进展[J]. 上海交通大学学报(医学版)202141(6):826-829.
Wei YZ Xue XM He B. Research progress in myocardial ischemia-reperfusion injury mediated by mitochondrial reactive oxygen species[J]. J Shanghai Jiao Tong Univ Med Sci202141(6):826-829.
2
Gong FF Vaitenas I Chris Malaisrie S,et al. Mechanical complications of acute myocardial infarction:a review[J]. JAMA Cardiol20216(3):341-349.
3
Reed GW Rossi JE Cannon CP. Acute myocardial infarction[J]. Lancet2017389(10065):197-210.
4
张 磊,张 军. 急性心肌梗死PCI灌注前静脉应用β受体阻滞剂效果的研究进展[J]. 中国循证心血管医学杂志202315(12):1388-1390.
Zhang L Zhang J. Research progress in efficacy of intravenous infusion of β-receptor blocker before PCI for acute myocardial infarction[J]. Chin J Evid Based Cardiovasc Med202315(12):1388-1390.
5
杨尚玉. 观察盐酸替罗非班联合心血管介入手术治疗急性心肌梗死疾病的效果[J]. 中国现代药物应用202418(16):11-14.
Yang SY. Observation on the effect of tirofiban hydrochloride combined with cardiovascular interventional surgery in the treatment of acute myocardial infarction[J]. Chin J Mod Drug Appl202418(16):11-14.
6
Panda AC. Circular RNAs act as miRNA sponges[J]. Adv Exp Med Biol20181087:67-79.
7
Kristensen LS Ebbesen KK Sokol M,et al. Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory[J]. Nat Commun202011(1):4551.
8
Ren K Li BY Jiang LQ,et al. circ_0023461 silencing protects cardiomyocytes from hypoxia-induced dysfunction through targeting miR-370-3p/PDE4D signaling[J]. Oxid Med Cell Longev20212021:8379962.
9
Zhao B Li GP Peng JJ,et al. CircMACF1 attenuates acute myocardial infarction through miR-500b-5p-EMP1 axis[J]. J Cardiovasc Transl Res202114(1):161-172.
10
Wang DM Tian LM Wang Y,et al. Circ_0001206 regulates miR-665/CRKL axis to alleviate hypoxia/reoxygenation-induced cardiomyocyte injury in myocardial infarction[J]. ESC Heart Fail20229(2):998-1007.
11
Zhang Y Li ZG Wang J,et al. CircTRRAP knockdown has cardioprotective function in cardiomyocytes via the signal regulation of miR-370-3p/PAWR axis[J]. Cardiovasc Ther20222022:7125602.
12
Gebert LFR MacRae IJ. Regulation of microRNA function in animals[J]. Nat Rev Mol Cell Biol201920(1):21-37.
13
Vishnoi A Rani S. MiRNA biogenesis and regulation of diseases:an overview[J]. Methods Mol Biol20171509:1-10.
14
Çakmak HA Demir M. MicroRNA and cardiovascular diseases[J]. Balkan Med J202037(2):60-71.
15
Wojciechowska A Braniewska A Kozar-Kamińska K. MicroRNA in cardiovascular biology and disease[J]. Adv Clin Exp Med201726(5):865-874.
16
Zhou SS Jin JP Wang JQ,et al. miRNAS in cardiovascular diseases:potential biomarkers,therapeutic targets and challenges[J]. Acta Pharmacol Sin201839(7):1073-1084.
17
Huang ZQ Wu SJ Kong FQ,et al. MicroRNA-21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway[J]. J Cell Mol Med201721(3):467-474.
18
Fang J Song XW Tian J,et al. Overexpression of microRNA-378 attenuates ischemia-induced apoptosis by inhibiting caspase-3 expression in cardiac myocytes[J]. Apoptosis201217(4):410-423.
19
Diener C Keller A Meese E. The miRNA–target interactions:An underestimated intricacy[J]. Nucleic Acids Research202452(4):1544-1557.
20
Li Z Xu H Liu X,et al. GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3[J]. Cell Death Dis202011(10):917.
21
Caño-Carrillo S Lozano-Velasco E Castillo-Casas JM,et al. The role of ncRNAs in cardiac infarction and regeneration[J]. J Cardiovasc Dev Dis202310(3):123.
22
Abbas N Perbellini F Thum T. Non-coding RNAs:emerging players in cardiomyocyte proliferation and cardiac regeneration[J]. Basic Res Cardiol2020115(5):52.
23
Yuan T Krishnan J. Non-coding RNAs in cardiac regeneration[J]. Front Physiol202112:650566.
24
胡林慧,潘 静,程 浩,等. 肝细胞癌中YARS1的表达及其对预后的影响[J]. Chin J Hepatol202533(2):151-158.
Hu LH Pan J Cheng H,et al. Expression of YARS1 in hepatocellular carcinoma and its impact on prognosis [J]. Chin J Hepatol202533(2):151-158.
25
Dong XX Dong XY Gao F,et al. Non-coding RNAs in cardiomyocyte proliferation and cardiac regeneration:Dissecting their therapeutic values[J]. J Cell Mol Med202125(5):2315-2332.
26
Braga L Ali H Secco I,et al. Non-coding RNA therapeutics for cardiac regeneration[J]. Cardiovasc Res2021117(3):674-693.
27
Yin LL Tang YH Jiang MH. Research on the circular RNA bioinformatics in patients with acute myocardial infarction[J]. J Clin Lab Anal202135(2):e23621.
28
Liu JY Dong WJ Gao CM,et al. Salvianolic acid B protects cardiomyocytes from ischemia/reperfusion injury by mediating circTRRAP/miR-214-3p/SOX6 axis[J]. Int Heart J202263(6):1176-1186.
29
Seco-Cervera M González-Rodríguez D Ibáñez-Cabellos JS,et al. Circulating miR-323-3p is a biomarker for cardiomyopathy and an indicator of phenotypic variability in Friedreich’s Ataxia patients[J]. Sci Rep20177(1):5237.
30
Pilbrow AP Cordeddu L Cameron VA,et al. Circulating miR-323-3p and miR-652:candidate markers for the presence and progression of acute coronary syndromes[J]. Int J Cardiol2014176(2):375-385.
31
Zhang JC Lang Y Guo LH,et al. MicroRNA-323a-3p promotes pressure overload-induced cardiac fibrosis by targeting TIMP3[J]. Cell Physiol Biochem201850(6):2176-2187.
32
Hanna A Frangogiannis NG. The role of the TGF-β superfamily in myocardial infarction[J]. Front Cardiovasc Med20196:140.
33
Huang SB Chen BJ Su Y,et al. Distinct roles of myofibroblast-specific Smad2 and Smad3 signaling in repair and remodeling of the infarcted heart[J]. J Mol Cell Cardiol2019132:84-97.
34
Jiang JJ Gu XP Wang HF,et al. Resveratrol improves cardiac function and left ventricular fibrosis after myocardial infarction in rats by inhibiting NLRP3 inflammasome activity and the TGF-β1/SMAD2 signaling pathway[J]. PeerJ20219:e11501.

Comments

PDF(5434 KB)

Accesses

Citation

Detail

Sections
Recommended

/