Fan Ming-Qi, Huang Chi-Bing, Gu Yan, Xiao Ya, Sheng Jin-Xin, Zhong Lin
J Exp Clin Cancer Res. 2013 Apr 18;32(1):21. doi: 10.1186/1756-9966-32-21.
Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC).
MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays.
MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells.
MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients.
越来越多的证据表明，微小RNA在癌症的发生、发展、转移过程中发挥着重要作用，并且可能成为癌症预后的有力生物标志物。本研究旨在确定微小RNA-20a（miR-20a）在肝细胞癌（HCC）中的临床及功能关联。
采用Taqman实时聚合酶链反应检测miR-20a。运用Kaplan-Meier法和Cox比例回归分析来确定miR-20a与患者生存率的关联。通过增殖和流式细胞术分析评估miR-20a对增殖的潜在作用。还通过荧光素酶报告基因检测确定miR-20a的直接靶基因。
原发性肝癌中miR-20a水平低于正常肝脏，肝移植（LT）后肝癌复发患者的miR-20a水平与未复发患者相比进一步降低（p = 0.001）。miR-20a表达较低的患者无复发生存期（RFS，对数秩检验p < 0.001）和总生存期（OS，对数秩检验p < 0.001）明显较差。多因素分析显示，较低的miR-20a是预后不良的独立预测因素。miR-20a的恢复可抑制HepG2和SMMC-7721细胞的增殖，并诱导细胞周期G1期阻滞和凋亡。随后的研究表明，miR-20a直接靶向髓细胞白血病序列1（Mcl-1），并降低肝癌细胞中Mcl-1的内源性蛋白水平。
HCC中miR-20a水平降低，且与HCC复发及预后相关。miR-20a的下调增加了肝癌细胞的增殖能力。我们的研究结果表明，miR-20a可能是肝癌患者生存的一个新潜在治疗靶点和生物标志物。
