目的:探讨在颈动脉粥样硬化(CAS)中circRNA-GRHPR的表达水平及临床意义。方法:随机选择在包头医学院第一附属医院神经内三科住院患者124例,根据颈动脉影像学检查是否存在动脉粥样硬化(AS)分为对照组和病例组。对照组30例患者,颈动脉中并未发现斑块;病例组94例患者,颈动脉中存在着斑块,这些斑块或是硬质的,或是软质的,又或是软硬混合的。应用实时荧光定量PCR(qRT-PCR)验证circRNA-GRHPR在细胞中具有差异化表达,深入分析circRNA-GRHPR在CAS中所起的作用。结果:CAS的发生与性别、年龄、收缩压、吸烟史、饮酒史、高血压病史、外周血circRNA-GRHPR表达水平均相关,且均为正相关(P<0.05);HDL-C与CAS相关,且为负相关(P<0.05)。病例组患者外周血circRNA-GRHPR表达水平高于对照组(P<0.05)。结论:CAS的发生与患者血清中circRNA-GRHPR的表达水平具有明显相关性,有可能成为AS改进诊断的工具和新治疗靶点,为早期干预措施铺平道路。
Objective: To investigate the expression levels and clinical significance of circRNA-GRHPR in carotid atherosclerosis (CAS). Methods: A total of 124 patients were randomly selected from the Third Department of Neurology, the First Affiliated Hospital of Baotou Medical College. These patients were divided into the control group and the case group based on whether they had atherosclerosis (AS) in the carotid artery as shown by imaging examinations. In the control group, 30 patients had no plaques found in the carotid arteries; in the case group, 94 patients had plaques in the carotid arteries, which were either hard, soft, or mixed. Real-time quantitative PCR (qRT-PCR) was used to verify differential expression of circRNA-GRHPR in cells and to further analyze the role of circRNA-GRHPR in CAS. Results: The occurrence of CAS was associated with gender, age, systolic blood pressure, smoking history, alcohol consumption history, hypertension history, and peripheral blood circRNA-GRHPR expression levels, all of which were positively correlated (P<0.05); HDL-C was associated with CAS but negatively correlated (P<0.05). The peripheral blood circRNA-GRHPR expression level in the case group was higher than that in the control group (P<0.05). Conclusion: The occurrence of CAS is significantly related to the expression levels of circRNA-GRHPR in patients′ serum, potentially serving as an improved diagnostic tool and a new therapeutic target for AS, paving the way for early intervention measures.
[1] Dai P, Yu HX, Wang ZX, et al.The relationship between severe extracranial artery stenosis or occlusion and cerebral small vessel disease in patients with large artery atherosclerotic cerebral infarction[J].Front Neurol, 2022, 13:1008319.
[2] Libby P.Inflammation in atherosclerosis[J].Nature, 2002, 420(6917):868-874.
[3] Stoll G, Bendszus M.Inflammation and atherosclerosis:Novel insights into plaque formation and destabilization[J].Stroke, 2006, 37(7):1923-1932.
[4] Coli S, Magnoni M, Sangiorgi G, et al.Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid arteries correlation with histology and plaque echogenicity[J].J Am Coll Cardiol, 2008, 52(3):223-230.
[5] Jeck WR, Sharpless NE.Detecting and characterizing circular RNAs[J].Nat Biotechnol, 2014, 32(5):453-461.
[6] Chen B, Ji F, Wen XN, et al.Circular RNA circ_ASAP2 promotes cell viability, migration, and invasion of gastric cancer cells by regulating the miR-770-5p/CDK6 axis[J].Int J Clin Exp Pathol, 2020, 13(11):2806-2819.
[7] Guo XF, Zhou QB, Su D, et al.Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis[J].Mol Cancer, 2020, 19(1):83.
[8] Jian XY, He H, Zhu JH, et al.Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340[J].Mol Cancer, 2020, 19(1):20.
[9] Hsiao KY, Lin YC, Gupta SK, et al.Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis[J].Cancer Res, 2017, 77(9):2339-2350.
[10] Li ZY, Huang C, Bao C, et al.Exon-intron circular RNAs regulate transcription in the nucleus[J].Nat Struct Mol Biol, 2015, 22(3):256-264.
[11] Tsai MC, Manor O, Wan Y, et al.Long noncoding RNA as modular scaffold of histone modification complexes[J].Science, 2010, 329(5992):689-693.
[12] Conn VM, Hugouvieux V, Nayak A, et al.A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation[J].Nat Plants, 2017, 3:17053.
[13] Chen L, Kong R, Wu C, et al.Circ-MALAT1 functions as both an mRNA translation brake and a microRNA sponge to promote self-renewal of hepatocellular cancer stem cells[J].Adv Sci(Weinh), 2020, 7(4):1900949.
[14] Zhu YJ, Zheng B, Luo GJ, et al.Circular RNAs negatively regulate cancer stem cells by physically binding FMRP against CCAR1 complex in hepatocellular carcinoma[J].Theranostics, 2019, 9(12):3526-3540.
[15] Zhang Z, Li LF, Shi HQ, et al.Role of Circular RNAs in Atherosclerosis through Regulation of Inflammation, Cell Proliferation, Migration, and Apoptosis:Focus on Atherosclerotic Cerebrovascular Disease[J].Medicina(Kaunas), 2023, 59(8):1461.
[16] 杨爽爽.GRHPR抑制肝细胞癌发展的生物学功能及其上游miRNA调控机制研究[D].郑州:郑州大学, 2022.
[17] Liu J, Hu SL, Chen LY, et al.Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets[J].Medrxiv, 2023:2023.11.30.23299247.
[18] Hou Y, Lin JF, Wang DY, et al.The circular RNA circ_GRHPR promotes NSCLC cell proliferation and invasion via interactions with the RNA-binding protein PCBP2[J].Clin Exp Pharmacol Physiol, 2021, 48(8):1171-1181.
[19] Heskett CW, Teafatiller T, Hennessey C, et al.Enteropathogenic Escherichia coli Infection Inhibits Intestinal Ascorbic Acid Uptake via Dysregulation of Its Transporter Expression[J].Dig Dis Sci, 2021, 66(7):2250-2260.
[20] 许泽美.PCBP2通过结合PARP1 mRNA稳定PARP1并参与Olaparib耐药过程[D].汕头:汕头大学, 2021.
[21] Mao ZY, Hine C, Tian X, et al.SIRT6 promotes DNA repair under stress by activating PARP1[J].Science, 2011, 332(6036):1443-1446.
[22] Huang YQ, Zhu W, Zhou J, et al.Navigating the Evolving Landscape of Primary Hyperoxaluria:Traditional Management Defied by the Rise of Novel Molecular Drugs[J].Biomolecules, 2024, 14(5):511.
[23] Kurakula K, Vos M, Otermin Rubio I, et al.The LIM-only protein FHL2 reduces vascular lesion formation involving inhibition of proliferation and migration of smooth muscle cells[J].PLoS One, 2014, 9(4):e94931.
[24] Li RC, Xu WD, Lei YL, et al.The risk of stroke and associated risk factors in a health examination population:a cross-sectional study[J].Medicine(Baltimore), 2019, 98(40):e17218.