Kılıç Nedret, Boyacıoğlu Özge, Saltoğlu Gamze Turna, Bulduk Erkut Baha, Kurt Gökhan, Korkusuz Petek
Department of Medical Biochemistry, Faculty of Medicine, Atılım University, Gölbaşı, Ankara, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Atılım University, Gölbaşı, Ankara, Turkey; Department of Bioengineering, Graduate School of Science and Engineering, Hacettepe University, Beytepe, Ankara, Turkey.
World Neurosurg. 2022 Nov;167:e1299-e1309. doi: 10.1016/j.wneu.2022.09.024. Epub 2022 Sep 9.
The thioredoxin system and microRNAs (miRNAs) are potential targets for both cancer progression and treatment. However, the role of miRNAs and their relation with the expression profile of thioredoxin system in brain tumor progression remains unclear.
In this study, we aimed to determine the expression profiles of redox components Trx-1, TrxR-1 and PRDX-1, and oncogenic miR-21, miR-23a/b and let-7a and oncosuppressor miR-125 in different brain tumor tissues and their association with increasing tumor grade. We studied Trx-1, TrxR-1, and PRDX-1 messenger RNA expression levels by quantitative real-time polymerase chain reaction and protein levels by Western blot and miR-23a, miR-23b, miR-125a, miR-21, and let-7a miRNA expression levels by quantitative real-time polymerase chain reaction in 16 glioma, 15 meningioma, 5 metastatic, and 2 benign tumor samples. We also examined Trx-1, TrxR-1, and PRDX-1 protein levels in serum samples of 36 patients with brain tumor and 37 healthy volunteers by enzyme-linked immunosorbent assay.
We found that Trx-1, TrxR-1, and PRDX-1 presented high messenger RNA expression but low protein expression in low-grade brain tumor tissues, whereas they showed higher protein expression in sera of patients with low-grade brain tumors. miR-23b, miR-21, miR-23a, and let-7a were highly expressed in low-grade brain tumor tissues and positively correlated with the increase in thioredoxin system activity.
Our findings showed that Trx-1, TrxR-1, miR-21, miR-23a/b, and let-7a might be used for brain tumor diagnosis in the clinic. Further prospective studies including molecular pathway analyses are required to validate the miRNA/Trx system regulatory axis in brain tumor progression.
硫氧还蛋白系统和微小RNA(miRNA)是癌症进展和治疗的潜在靶点。然而,miRNA在脑肿瘤进展中的作用及其与硫氧还蛋白系统表达谱的关系仍不清楚。
在本研究中,我们旨在确定氧化还原成分Trx-1、TrxR-1和PRDX-1以及致癌性miR-21、miR-23a/b和let-7a以及抑癌性miR-125在不同脑肿瘤组织中的表达谱,以及它们与肿瘤分级增加的相关性。我们通过定量实时聚合酶链反应研究Trx-1、TrxR-1和PRDX-1信使核糖核酸表达水平,通过蛋白质印迹研究蛋白质水平,并通过定量实时聚合酶链反应研究16例神经胶质瘤、15例脑膜瘤、5例转移瘤和2例良性肿瘤样本中miR-23a、miR-23b、miR-125a、miR-21和let-7a miRNA表达水平。我们还通过酶联免疫吸附测定法检测了36例脑肿瘤患者和37名健康志愿者血清样本中Trx-1、TrxR-1和PRDX-1的蛋白质水平。
我们发现Trx-1、TrxR-1和PRDX-1在低级别脑肿瘤组织中呈现高信使核糖核酸表达但低蛋白质表达,而在低级别脑肿瘤患者血清中它们显示出较高的蛋白质表达。miR-23b、miR-21、miR-23a和let-7a在低级别脑肿瘤组织中高表达,并且与硫氧还蛋白系统活性的增加呈正相关。
我们的研究结果表明,Trx-1、TrxR-1、miR-21、miR-23a/b和let-7a可能在临床上用于脑肿瘤诊断。需要进一步的前瞻性研究,包括分子途径分析,以验证miRNA/Trx系统在脑肿瘤进展中的调控轴。