长链非编码RNA FER1L4在肝细胞癌中调节miR-106a-5p发挥抑癌因子作用的研究

Long non-coding RNA fer-1-like protein 4 acts as a tumor suppressor via miR-106a-5p and predicts good prognosis in hepatocellular carcinoma

目的:探讨长链非编码RNA FER1L4(lncRNA FER1L4)调节miR-106a-5p的表达影响肝癌细胞增殖、迁移、侵袭能力的可能机制及其临床意义。方法:收集2017~2019年阜阳市第五人民医院及大连大学附属中山医院36例肝细胞癌患者手术标本,采用荧光定量PCR技术(RT-qPCR)分析肝癌细胞和癌旁正常肝细胞中lncRNA FER1L4和miR-106a-5p的表达情况。同时采用RT-qPCR分析肝癌细胞系Huh-7、HepG2和正常肝细胞系L-02中lncRNA FER1L4和miR-106a-5p的表达情况。采用CCK-8法、细胞划痕及集落形成实验等方法测定细胞的增殖、转移和成瘤能力。结果:与正常组织相比,lncRNA FER1L4在肝癌组织中表达较低(P<0.05),而miR-106a-5p表达较高(P<0.05),且两者呈负相关(P<0.0001,R2=0.376);与对照组相比,下调FER1L4肝癌细胞的增殖能力增加(P<0.05),敲除FER1L4肝癌细胞的迁移和侵袭能力增加(P<0.05);与对照组相比,转染FER1L4 siRNA的肿瘤细胞中miR-106a-5p的表达增高(P<0.05),敲除miR-106a-5p的肿瘤细胞中FER1L4的表达增高(P<0.05),两者之间存在相互抑制的关系。结论:lncRNA FER1L4通过抑制miR-106a-5p的表达对肝细胞癌产生抑制作用,单独或联合检测lncRNA FER1L4和miR-106a-5p可能预测肝癌的临床预后。

Objective:To investigate the possible mechanism of long-chain non-coding RNA FER1L4(lncRNA FER1L4)regulating the expression of miR-106a-5p and affecting the proliferation,migration and invasion ability of hepatoma cells,as well as its clinical significance.Methods:From 2017 to 2019,surgical specimens from 36 patients with hepatocellular carcinoma were collected at Fuyang Fifth People's Hospital and Zhongshan Hospital affiliated with Dalian University,and the expression of lncRNA FER1L4 and miR-106a-5p in hepatoma cells and adjacent normal hepatocytes was analyzed by real-time quantitative PCR(RT-qPCR).The expression of lncRNA FER1L4 and miR-106a-5p in hepatoma cell lines Huh-7,HepG2,and normal hepatocyte line L-02 was studied using RT-qPCR.The CCK-8 technique,cell scratch,and colony formation assay were employed to measure cell proliferation,metastasis,and tumorigenic capacity.Results:Compared with normal tissues,lncRNA FER1L4 expression was lower(P<0.05)and miR-106a-5p expression was greater(P<0.05),and the two were negatively linked(P<0.0001,R2=0.376).The value-added ability of down-regulated FER1L4 hepatoma cells was boosted(P<0.05)compared to the control group,as was the migration and invasion capacity of deletion FER1L4 hepatoma cells(P<0.05).The expression of miR-106a-5p in tumor cells transfected with FER1L4 siRNA was enhanced(P<0.05)compared to the control group,as did the expression of FER1L4 in tumor cells knocked out of miR-106a-5p(P<0.05),and there was a mutual inhibitory connection between the two.Conclusion:By suppressing the expression of miR-106a-5p,lncRNA FER1L4 has an inhibitory impact on hepatocellular carcinoma,and the detection of lncRNA FER1L4 and miR-106a-5p alone or in combination may predict the clinical prognosis of liver cancer.