MiR-18B-5p调节BTG3及其下游信号通路促进肝细胞癌的发生发展

目的 本研究旨在探讨miR-18B-5p在肝癌中的作用及其机制。方法 检测miR-18B-5p在肝癌患者血清中的表达水平，对其临床意义进行分析。下调miR-18B-5p表达水平，检测miR-18B-5p在肝癌细胞系增殖、迁移和侵袭中的作用，用实时荧光定量聚合酶链反应和荧光素酶报告法探讨其作用机制。结果 低miR-18B-5p表达组患者生存率高于高miR-18B-5p表达组（P＜0.05），多因素分析结果显示，miR-18B-5p的表达水平（RR:2.064，95%CI:1.522~2.800）和年龄（RR:1.762，95%CI:1.347~2.305）是患者生存的影响因素，HepG2细胞表达的miR-18B-5p水平高于Bel-7402组、MHCC97组和Hep3B组（P＜0.05），Si-miR-18B-5p细胞系的Si-miR-18B-5p表达和细胞增殖低于HepG2细胞系（P＜0.05），在Si-miR-18B-5p细胞系miR-18B-5p下调，细胞迁移和侵袭能力低于HepG2细胞系（P＜0.05），Si-miR-18B-5p细胞中BTG3的mRNA表达高于HepG2细胞系（P＜0.05），BTG3 WT相对荧光素活性低于BTG3 Mut（P＜0.05）。结论 MiR-18B-5p可作为肝癌新的治疗靶点和预后标志物。

MiR-18B-5p regulates BTG3 and downstream signaling pathways to promote the development of hepatocellular carcinoma

Objective To explore the role and the mechanism of miR-18B-5p in hepatocellular carcinoma(HCC).Methods The expression levels of miR-18B-5p were measured in serum of patients with HCC, and its clinical relevance was analyzed. The miR-18B-5p level was down-regulated and the role of miR-18B-5p in the proliferation, migration and invasion in HCC cell lines was examined. In addition, its mechanism was detected by qRT-PCR and luciferase reporters.Results The survival rate of patients in low miR-18B-5p expression group was higher than that in high miR-18B-5p expression group(P＜0.05). Multivariate analysis showed that the expression level of miR-18B-5p(RR: 2.064, 95%CI: 1.522-2.800) and age(RR: 1.762, 95%CI: 1.347-2.305) were the influencing factors of survival. The level of miR-18B-5p expressed by HepG2 cells was higher than that in BEL-7402 group, MHCC97 group and Hep3B group(P＜0.05). The expression of Si-miR-18B-5p and cell proliferation of Si-miR-18B-5p cell line were lower than those of HepG2 cell line(P＜0.05). In Si-miR-18B-5p cell line, miR-18B-5p was down-regulated, and the ability of cell migration and invasion was lower than that of HepG2 cell line(P＜0.05). The mRNA expression of BTG3 in Si-miR-18B-5p cell line was higher than that of HepG2 cell line(P＜0.05). The relative fluorescein activity of BTG3 WT was lower than that of BTG3 Mut(P＜0.05).Conclusion MiR-18B-5p may be a new therapeutic target and prognostic biomarker for HCC.