Department of Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Eur Rev Med Pharmacol Sci. 2018 Mar;22(5):1277-1285. doi: 10.26355/eurrev_201803_14468.
MiR-155 has been shown to be up-regulated in hepatocellular carcinoma (HCC) patients. B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (BIM) regulates cell proliferation and apoptosis, as its down-regulation is involved in HCC onset. Transcriptional factor FoxO3a mediates BIM expression and is related to HCC pathogenesis. Bioinformatics analysis showed targeted regulation of FoxO3a by miR-155. This study aims to investigate whether miR-155 plays a role in mediating FoxO3a/BIM signal pathway and HCC occurrence.
HCC patients were collected for tumor and adjacent tissues, in which microRNA-155 (miR-155) and FoxO3a expressions were examined. In vitro cultured HCCLM3, HepG2 and L-02 cells were tested for basal apoptotic rate by flow cytometry and were compared for miR-155 and FoxO3a expression. Dual-luciferase reporter gene assay demonstrated the targeted relationship between miR-155 and FoxO3a. HCCLM3 cells were treated with miR-155 inhibitor and/or FoxO3a-pMD18-T. Cell apoptosis and proliferation were examined by using flow cytometry and MTT assays, respectively. Western blot and spectrometry assay were employed to quantify the FoxO3a, BIM expressions, and caspase activity.
Compared to adjacent tissues, HCC tissues had significantly higher miR-155 and significantly lower FoxO3a expression (p<0.05). HCCLM3 and HepG2 cells had significantly lower FoxO3a expression and basal apoptotic rate compared to L02 cells, whilst miR-155 level was significantly higher (p<0.05). MiR-155 targeted and inhibited 3'-UTR of FoxO3a, increasing BIM expression, caspase-3, and caspase-9 activities, and enhancing cell apoptosis and weakening proliferation.
HCC tissues elevated the miR-155 and suppressed the FoxO3a expressions. MiR-155 targeted and inhibited FoxO3a expression to suppress the BIM, depress caspase-3 and caspase-9 activities, therefore inhibiting the HCC cell apoptosis and facilitating proliferation.
miR-155 在肝细胞癌（HCC）患者中呈上调表达。B 细胞淋巴瘤-2（Bcl-2）相互作用的细胞死亡介体（BIM）调节细胞增殖和凋亡，其下调与 HCC 的发生有关。转录因子 FoxO3a 介导 BIM 的表达，与 HCC 的发病机制有关。生物信息学分析显示 miR-155 靶向调节 FoxO3a。本研究旨在探讨 miR-155 是否在调节 FoxO3a/BIM 信号通路和 HCC 发生中发挥作用。
收集 HCC 患者的肿瘤和相邻组织，检测 microRNA-155（miR-155）和 FoxO3a 的表达。体外培养 HCCLM3、HepG2 和 L-02 细胞，通过流式细胞术检测基础凋亡率，并比较 miR-155 和 FoxO3a 的表达。双荧光素酶报告基因实验证实 miR-155 与 FoxO3a 之间的靶向关系。用 miR-155 抑制剂和/或 FoxO3a-pMD18-T 处理 HCCLM3 细胞。分别通过流式细胞术和 MTT 法检测细胞凋亡和增殖。采用 Western blot 和光谱法检测 FoxO3a、BIM 表达和 caspase 活性。
与相邻组织相比，HCC 组织中 miR-155 表达显著升高，FoxO3a 表达显著降低（p<0.05）。与 L02 细胞相比，HCCLM3 和 HepG2 细胞中 FoxO3a 表达和基础凋亡率显著降低，而 miR-155 水平显著升高（p<0.05）。miR-155 靶向并抑制 FoxO3a 的 3'-UTR，增加 BIM 表达、caspase-3 和 caspase-9 的活性，增强细胞凋亡，减弱增殖。
HCC 组织中 miR-155 表达升高，FoxO3a 表达下调。miR-155 靶向并抑制 FoxO3a 表达，抑制 BIM、降低 caspase-3 和 caspase-9 的活性，从而抑制 HCC 细胞凋亡，促进增殖。
