miR-145/HMGB3轴对胆囊癌患者的诊断和预后及对胆囊癌细胞凋亡的影响  

Effect of MiR-145/HMGB3 Axis on Diagnosis and Prognosis of Patients with Gallbladder Cancer and Apoptosis of Gallbladder Cancer Cells

作　　者：杨艺萱 崔大鹏[1] 郭丹 李紫宣 冯志林 宋雅琪 YANG Yixuan;CUI Dapeng;GUO Dan(Department of Hepatobiliary,the First Affiliated Hospital of Hebei North University,Hebei 075000,China)

机构地区：[1]河北北方学院附属第一医院肝胆外科,张家口075000

出　　处：《医学研究杂志》2024年第12期98-104,共7页Journal of Medical Research

基　　金：河北省医学科学研究课题计划项目(20220605)。

摘　　要：目的探讨血清miR-145和高迁移率族蛋白B3(high mobility group box 3,HMGB3)在胆囊癌(gallbladder cancer,GBC)患者中的表达水平及其与疾病进展的相关性,并验证miR-145对HMGB3表达及GBC细胞增殖和凋亡的影响,评估作为潜在的诊断和预后生物学标志物的可行性。方法选择2018年9月~2022年6月河北北方学院附属第一医院收治的90例胆囊癌患者作为疾病组,40名健康体检者为正常对照组。检测两组血清miR-145和HMGB3的表达水平;比较不同临床病理特征与miR-145和HMGB3表达水平的关系;受试者操作特征(receiver operating characteristic,ROC)曲线分析血清miR-145和HMGB3的诊断价值;采用Kaplan-Meier生存曲线评估不同miR-145和HMGB3表达水平患者的3年生存率。采用CCK-8实验和流式细胞术分析miR-145对胆囊癌细胞增殖和凋亡的影响;Western blot法检测细胞蛋白表达水平;流式细胞术检测各组凋亡率;通过双荧光素酶报告基因实验验证miR-145与HMGB3的直接相互作用。结果胆囊癌患者血清中miR-145表达水平显著降低(P<0.05),而HMGB3的表达水平显著上升(P<0.05)。血清miR-145和HMGB3的表达水平与分化程度、淋巴结转移和TNM分期有关(P<0.05)。ROC曲线分析结果显示,血清miR-145和HMGB3具有较高的诊断价值;Kaplan-Meier生存曲线分析结果表明,miR-145高表达亚组的3年生存率高于低表达亚组(P<0.05),HMGB3低表达亚组的3年生存率显著高于高表达亚组(P<0.05)。在体外实验中,miR-145过表达可抑制GBC细胞增殖,显著增加GBC-SD细胞Bax的蛋白表达水平(P<0.05),降低Bcl-2蛋白的表达(P<0.05),降低HMGB3蛋白表达(P<0.05),增加GBC-SD细胞凋亡率。双荧光素酶报告基因实验结果表明,HMGB3是miR-145的靶标。结论在胆囊癌中,miR-145的下调与HMGB3的上调存在显著关联,且与疾病的严重程度相关。miR-145的过表达能显著抑制胆囊癌细胞的增殖和促进凋亡,其作用机制可能通过直接靶向HMGB3实现Objective To investigate the expression levels of serum miR-145 and HMGB3 in patients with gallbladder cancer(GBC)and their correlation with disease progression,verify the effects of miR-145 on HMGB3 expression and the proliferation and apoptosis of GBC cells,and evaluate its feasibility as a potential diagnostic and prognostic biomarker.Methods Ninety patients with gallbladder cancer admitted to the First Affiliated Hospital of Hebei North University from September 2018 to June 2022 were selected as the disease group,and 40healthy subjects were selected as the normal control group.The expression levels of serum miR-145 and HMGB3 in two groups were detected.The relationship between different clinicopathological features and the expression levels of miR-145 and HMGB3 was compared.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum miR-145 and HMGB3;Kaplan-Meier survival curve was used to evaluate the 3-year survival rate of patients with different miR-145 and HMGB3 expression levels.The effects of miR-145 on proliferation and apoptosis of GBC cells were analyzed by CCK-8 assay and flow cytometry.The protein expression was detected by Western blot.The apoptosis rate of each group was detected by flow cytometry.The direct interaction between miR-145 and HMGB3 was verified by double luciferase reporter gene assay.Results The expression level of miR-145 in serum of patients with GBC was significantly decreased(P<0.05),while the expression level of HMGB3 was significantly increased(P<0.05).The expressions of serum miR-145 and HMGB3 were correlated with differentiation degree,lymph node metastasis and TNM stage(P<0.05).ROC curve analysis showed that serum miR-145 and HMGB3had high diagnostic value.Kaplan-Meire survival curve analysis showed that the 3-year survival rate of miRNA-143high expression subgroup was higher than that of low expression subgroup(P<0.05),and the 3-year survival rate of HMGB3 low expression subgroup was significantly higher than that of high expression sub

关 键 词：胆囊癌 MIR-145 高迁移率族蛋白B3 凋亡 病理特征 预后 

分 类 号：R545[医药卫生—心血管疾病]