miR-155-5p在肝细胞癌中的表达及其作用机制

The role of miR-155-5p in liver cancer and its mechanism

目的:初步探讨microRNA-155-5p(miR-155-5p)在原发性肝细胞癌(HCC)中的表达及作用,验证其对SRY核转录因子6(SOX6)的可能靶向调控作用,为HCC的靶向治疗提供新理论依据。方法:收集2017年1月至2019年10月在四川大学华西医院金堂医院胆外科接受手术切除的26例HCC患者的肿瘤组织和癌旁组织的样本。采用实时定量PCR(qRT-PCR)检测miR-155-5p和SOX6在不同HCC细胞系的表达情况;采用CCK-8法、划痕实验及Transwell实验观察miR-155-5p对HepG2细胞增殖、迁移和侵袭能力的影响;采用双荧光素报告基因验证miR-155-5p对SOX6的靶向调控作用。结果:与癌旁组织/正常细胞相比,肿瘤组织/HCC系细胞中miR-155-5p表达明显升高(P<0.01),而SOX6的表达量与癌旁组织相比显著下降(P<0.01);与miR-155-5p+NC组相比,miR-155-5p+SOX6组细胞凋亡率显著上升,细胞增殖,迁移以及侵袭明显抑制(P<0.05),此外,与Mut-SOX6-3转染的细胞相比,miR-155-5p和WT-SOX6-3'UTR共转染可明显抑制萤光素酶活性(P<0.01)。结论:miR-155-5p在HCC中高表达,且可促进HepG2细胞增殖、迁移和侵袭,其机制可能与miR-155-5p通过调控SOX6的表达来影响肝细胞癌的进展有关。

Objective:To Preliminary study on the expression and role of microRNA-155-5p(miR-155-5p)in Hepatocellular carcinoma(HCC),and verify its possible targeted regulation of SRY nuclear transcription factor 6(SOX6).Targeted therapy provides new theoretical basis.Methods:Samples of tumor tissues and adjacent tissues from 26 patients with primary hepatocellular carcinoma(HCC)who underwent surgical resection at Jintang Hospital of West China Hospital of Sichuan University from January 2017 to October 2019 were collected.Real-time quantitative PCR(qRT-PCR)was used to detect the expression of miR-155-5p and SOX6 in HCC and different HCC cell lines;CCK-8 method,scratch test and Transwell test were used to observe the proliferation of miR-155-5p on HepG2 cells Effect of miR-155-5p on SOX6 by dual luciferin reporter gene.Results:Compared with adjacent tissues/normal cells,the expression of miR-155-5p in tumor tissues/HCC cells was significantly increased(P<0.01),while the expression level of SOX6 was significantly decreased compared with adjacent tissues(P<0.01).Compared with miR-155-5p+NC,the apoptosis rate of miR-155-5p+SOX6 group increased significantly,and cell proliferation,migration and invasion were significantly inhibited(P<0.01).In addition,compared with Mut-SOX6-3 transfected cells,Co-transfection of miR-155-5p and WT-SOX6-3'UTR could significantly inhibit luciferase activity(P<0.01).Conclusion:miR-155-5p is highly expressed in HCC and can promote the proliferation,migration and invasion of HepG2 cells.The mechanism may be related to miR-155-5p affecting the progression of hepatocellular carcinoma by regulating the expression of SOX6,this provides new targets for the treatment of liver cancer.