【摘要】 目的 探讨miR-590-5p、DNA损伤检查点蛋白调节子1(mediator of DNA damage checkpoint 1, MDC1)在高级别胶质瘤（high-grade glioma, HGG）组织中的表达及与胶质瘤病人术后放疗效果的关系，并明确二者对胶质瘤细胞增殖、凋亡的影响。方法 选取2019年1月至2021年2月河北北方学院附属第一医院64例HGG患者，评估放疗效果。实时荧光定量PCR(qRT-PCR)法检测miR-590-5p水平，免疫组织化学染色检测MDC1表达情况，分析miR-590-5p、MDC1表达与胶质瘤病人术后放疗效果的关系，多因素Logistic回归分析影响HGG患者术后放疗效果的因素；体外培养胶质瘤U87MG细胞，并分别转染miR-590-5p mimic、MDC1-shRNA及其阴性对照，CCK-8法和流式细胞术分别检测细胞增殖和凋亡；构建裸鼠移植瘤模型，观察过表达miR-590-5p和敲低MDC1对肿瘤生长的影响。结果 MDC1在HGG组织中的表达较正常脑组织中升高，mi R-590-5p表达较正常脑组织降低，二者表达水平呈负相关；MDC1表达升高、miR-590-5p表达降低，其放疗效果越差；Logistic回归分析显示，MDC1高表达、miR-590-5p低表达均是影响HGG患者放疗效果的危险因素。过表达miR-590-5p和敲低MDC1后，U87MG细胞增殖力降低，凋亡率升高，移植瘤体积和重量下降，Ki-67阳性细胞比例减少。过表达miR-590-5p后MDC1蛋白表达明显下降。结论 HGG组织中miR-590-5p呈低表达，MDC1呈高表达，二者表达与HGG的发生和患者术后放疗效果关系密切；过表达miR-590-5p和敲低MDC1表达可抑制胶质瘤细胞增殖并促进凋亡。更多还原

【Abstract】 Objective To investigate the expression levels of miR-590-5p and Mediator of DNA Damage Checkpoint 1(MDC1) in high-grade glioma(HGG) tissues, their relationship with the effects of postoperative radiotherapy in glioma patients, and to explore their impact on the proliferation and apoptosis of glioma cells. Methods Sixty-four HGG patients who received treatment at The First Affiliated Hospital of Hebei North University from January 2019 to February 2021 were selected for this study. The efficacy of postoperative radiotherapy was evaluated in these patients. The expression level of miR-590-5p was detected using the quantitative real-time PCR(qRT-PCR) method, while the expression of MDC1 was determined by immunohistochemical staining. We analyzed the relationship between the expression levels of miR-590-5p and MDC1 and the effectiveness of postoperative radiotherapy in glioma patients. Multivariate logistic regression analysis was employed to identify factors influencing the outcome of postoperative radiotherapy in HGG patients. In vitro, glioma U87MG cells were cultured and transfected with miR-590-5p mimic, MDC1-shRNA, and their respective negative controls. Cell proliferation and apoptosis were assessed using CCK-8 and flow cytometry. Additionally, a nude mouse transplanted tumor model was established to observe the effects of overexpressing miR-590-5p and knocking down MDC1 on tumor growth. Results In HGG tissues, MDC1 expression was higher compared to normal brain tissue, while miR-590-5p expression was lower. Notably, the expressions of MDC1 and miR-590-5p were negatively correlated. Univariate analysis results indicated that patients with higher MDC1 expression and lower miR-590-5p expression experienced less effective radiotherapy outcomes. Logistic regression analysis identified high MDC1 expression and low miR-590-5p expression as risk factors impacting the efficacy of radiotherapy in HGG patients. Following the overexpression of miR-590-5p and knockdown of MDC1 in U87MG cells, there was a decrease in OD value and an increase in apoptosis rate. In the tumor graft model, both tumor volume and weight were reduced, and the proportion of Ki67 positive cells decreased. Additionally, MDC1 protein expression significantly decreased after miR-590-5p was overexpressed. Conclusion The expression level of miR-590-5p in HGG tissue is low, while the expression of MDC1 is high. These expression levels are closely associated with the development of HGG and the efficacy of postoperative radiotherapy. Overexpressing miR-590-5p and knocking down MDC1 expression have been observed to inhibit proliferation and promote apoptosis in glioma cells.更多还原