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微小RNA-138在肝内胆管癌中的表达及生物功能研究OA

The expression and biological function of microRNA-138 in intrahepatic cholangiocarcinoma

中文摘要英文摘要

目的 分析微小RNA-138(miR-138)在肝内胆管癌(ICC)中的表达及其对ICC细胞生物学功能的影响.方法 回顾性收集2018年6月至2021年6月郑州人民医院52例ICC手术患者的癌组织及癌旁组织,采用qRT-PCR检测miR-138的表达水平,并分析miR-138与ICC患者病理特征及预后的关系.培养人ICC细胞系(HuCCT1和RBE)及人正常肝内胆管细胞系HIBEC,利用脂质体转染技术转染miR-138 mimics,采用MTT法、流式细胞术及Transwell法检测细胞增殖、凋亡、周期及迁移和侵袭情况,Western blotting检测相关蛋白的表达,双荧光素酶实验验证miR-138与FOXC1的靶向关系.结果 ICC组织中miR-138表达水平明显低于癌旁组织(P<0.05),且与ICC患者TNM分期、淋巴结转移、血管侵犯及预后有关(均P<0.05).ICC细胞(HuCCT1和RBE)中,miR-138的表达水平明显低于HIBEC细胞(P<0.05).上调miR-138后,ICC细胞的增殖、迁移、侵袭能力和S期细胞数明显降低,凋亡率明显升高(P<0.05).Western blotting检测发现,上调miR-138后,ICC细胞内的Bax和E-cadherin蛋白水平明显升高,Bcl-2、CDK2、Cyclin D1、MMP-2、MMP-9和Vimentin蛋白水平明显降低(均P<0.05).双荧光素酶实验证实miR-138与FOXC1存在靶向关系.结论 miR-138在ICC中低表达,且与ICC的发生、发展及不良预后有关,其作用机制可能与靶向调控FOXC1有关.

Objective To analyze the expression of microRNA-138(miR-138)in intrahepatic cholangiocarcinoma(ICC)and explore the effect of miR-138 on the biological function of ICC cells.Methods The ICC tissues and the adjacent tissues from 52 patients undergoing ICC surgery in Zhengzhou People's Hospital between June 2018 and June 2021 were retrospectively collected.The expression of miR-138 was detected by qRT-PCR,and the relationship between miR-138 and the pathological features and prognosis of ICC patients were analyzed.To culture human ICC cell line(HuCCT1 and RBE)and human normal intrahepatic bile duct cell line(HIBEC),and transfected with miR-138 mimics by liposome transfection technique.Cell proliferation,apoptosis,cycle,migration and invasion were detected by MTT,flow cytometry and Transwell methods.Western blotting was used to detect the expression of related proteins.Dual luciferase assay were used to analyze the targeting relationship between miR-138 and FOXC1.Results The expression level of miR-138 in ICC cancer tissues was significantly lower than that in adjacent tissues(P<0.05).MiR-138 was related to TNM stage,lymph node metastasis,vascular invasion and prognosis of ICC patients(P<0.05).The expression level of miR-138 in ICC cells(HuCCT1 and RBE)was significantly lower than that in HIBEC cells(all P<0.05).After up-regulation of miR-138,the proliferation,migration and invasion ability of ICC cells and the proportion of S phase cells were significantly reduced,and the apoptosis rate was significantly increased(P<0.05).Western blotting analysis showed that after up-regulation of miR-138,the expression levels of Bax and E-cadherin in ICC cells were significantly increased,while the expression levels of Bcl-2,CDK2,Cyclin D1,MMP-2,MMP-9 and Vimentin were significantly decreased(all P<0.05).Dual luciferase assay confirmed the targeting relationship between miR-138 and FOXC1.Conclusion The low expression of miR-138 in ICC tissues and cells is related to the occurrence,development and poor prognosis of ICC.The underlying mechanism may be related to the targeted regulation of FOXC1.

仝麟龙;张俊杰;秦靖宜;李文奇

郑州人民医院普外三科,河南 郑州 450000郑州人民医院普外三科,河南 郑州 450000郑州人民医院普外三科,河南 郑州 450000郑州人民医院普外三科,河南 郑州 450000

医药卫生

肝内胆管癌微小RNA-138TNM分期淋巴结转移血管侵犯预后生物学功能

intrahepatic cholangiocarcinomamicroRNA-138TNM stagelymph node metastasisvascular invasionprognosisbiological function

《肝胆胰外科杂志》 2026 (7)

470-477,8

10.11952/j.issn.1007-1954.2026.07.003

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