摘要
目的探讨长链非编码RNA(lncRNA)MIR100HG在肝细胞癌组织中的表达及临床意义,并验证lncRNA MIR100HG与hsa-miR-2355-3p的调控关系及其对肝细胞癌细胞迁移和侵袭能力的影响。方法采用实时荧光定量PCR检测cDNA芯片中lncRNA MIR100HG和hsa-miR-2355-3p的表达;分析肝细胞癌组织中lncRNA MIR100HG相对表达水平与患者临床病理参数及预后的关系;采用双荧光素酶报告实验验证lncRNA MIR100HG与hsa-miR-2355-3p之间的调控关系;通过Transwell实验验证lncRNA MIR100HG与hsa-miR-2355-3p对肝细胞癌细胞系HepG2迁移和侵袭能力的影响。结果相较于hsa-miR-2355-3p在肝细胞癌组织中的表达下调,lncRNA MIR100HG在肝细胞癌组织中异常高表达,肝细胞癌组织中lncRNA MIR100HG高表达组中肿瘤最大径越大,更倾向于淋巴结转移、血管侵犯、肿瘤远处转移;血清γ-谷氨酰基转移酶水平越高,肿瘤TNM分期越高,更倾向于肿瘤复发。在TNMⅠ~Ⅳ期、TNMⅠ期、TNMⅡ期的肝细胞癌患者中,lncRNA MIR100HG高表达组患者总体生存率和无复发生存率较低表达组显著降低。多因素回归分析显示,lncRNA MIR100HG异常高表达是肝细胞癌患者预后不良的独立危险因素。Transwell实验表明,下调hsa-miR-2355-3p能够逆转lncRNA MIR100HG沉默介导的对肝细胞癌侵袭和迁移的抑制作用;双荧光素酶报告实验表明,lncRNA MIR100HG可能与hsa-miR-2355-3p存在物理学上的结合位点。结论lncRNA MIR100HG异常高表达与肝细胞癌恶性生物学行为密切相关,其可能通过介导hsa-miR-2355-3p促进肝细胞癌迁移和侵袭。
Objective To investigate the expression and clinical significance of long non-coding RNA(lncRNA)MIR100HG in hepatocellular carcinoma tissues,and to verify the regulatory relationship of lncRNA MIR100HG and hsa-miR-2355-3p and its effect on migration and invasion ability of hepatocellular carcinoma cell.Methods Real-time fluorescence quantitative PCR was used to detect the expressions of lncRNA MIR100HG and hsa-miR-2355-3p in cDNA chips;the correlation between the lncRNA MIR100HG relative expression level in hepatocellular carcinoma tissues and clinicopathological parameters as well as prognosis were analyzed,dual luciferase reporter assay was applied to verify the regulatory relationship between lncRNA MIR100HG and hsa-miR-2355-3p,the effects of lncRNA MIR100HG and hsa-miR-2355-3p on the migration and invasion of hepatocellular carcinoma cell line HepG2 were utilized by Transwell assay.Results Compared with the down-regulated expression of hsa-miR-2355-3p in hepatocellular carcinoma tissues,lncRNA MIR100HG was abnormally highly expressed in hepatocellular carcinoma tissues.In hepatocellular carcinoma tissues,lncRNA MIR100HG high-expression group had larger tumor maximum diameter,and were more prone to lymph node metastasis,vascular invasion,and distant tumor metastasis.The higher the level of serum gamma-glutamyl transpeptidase,the higher the TNM stage of tumor and the more inclined to tumor recurrence.In patients with hepatocellular carcinoma in TNM-stageⅠtoⅣ,TNM-stageⅠand TNM-stageⅡ,the overall survival rate and relapse-free survival rate of patients in the high expression group of lncRNA MIR100HG were significantly lower than those in the low expression group.Multivariate regression analysis showed that abnormally high expression of lncRNA MIR100HG was an independent risk factor for poor prognosis in patients with hepatocellular carcinoma.Transwell experiments showed that down-regulation of hsa-miR-2355-3p could reverse lncRNA MIR100HG silencing-mediated inhibition of invasion and migration of hepatocellular carcinoma cell;Dual luciferase reporter experiments indicated that lncRNA MIR100HG may interact with hsa-miR-2355-3p physically.Conclusion The abnormally high expression of lncRNA MIR100HG is closely related to the malignant biological behavior of hepatocellular carcinoma,which may promote hepatocellular carcinoma migration and invasion by mediating hsa-miR-2355-3p.
作者
王霞
WANG Xia(Department of Medical Laboratory Center,Huai′an First Hospital Affiliated to Nanjing Medical University,Huai′an,Jiangsu 223300,China)
出处
《国际检验医学杂志》
CAS
2024年第3期365-372,共8页
International Journal of Laboratory Medicine
关键词
肝细胞癌
预后
迁移
hepatocellular carcinoma
prognosis
migration
