Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma.
Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma.
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microRNA-20a表达减少促进癌细胞增殖并预测肝细胞癌的不良生存
DOI：
10.1186/1756-9966-32-21
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发表时间：
2013-04-18
期刊：
影响因子：
--
通讯作者：
Zhong L
中科院分区：
文献类型：
--
作者：
Fan MQ;Huang CB;Gu Y;Xiao Y;Sheng JX;Zhong L
越来越多的证据表明microRNA在肿瘤的发生、发展、转移中起重要作用，并可能成为肿瘤预后的生物标志物。本研究的目的是确定microRNA-20 a（miR-20 a）在肝细胞癌（HCC）中的临床和功能相关性。使用Taqman实时聚合酶链反应检测miR-20 a。Kaplan-Meier和考克斯比例回归分析用于确定miR-20 a与患者生存期的相关性。通过细胞增殖和流式细胞术分析miR-20 a对细胞增殖的潜在作用。还通过荧光素酶报告基因测定鉴定了miR-20 a的直接靶基因。miR-20 a在原发性HCC中低于正常肝脏，并且在肝移植（LT）后HCC复发的患者中与未复发的患者相比进一步降低（p = 0.001）。miR-20 a表达较低的患者无复发生存期（RFS，Log rank p < 0.001）和总生存期（OS，Log rank p < 0.001）显著较差。多因素分析显示，较低的miR-20 a是预后不良的独立预测因子。miR-20 a恢复可抑制HepG 2和SMMC-7721细胞增殖，诱导细胞周期G1期阻滞和凋亡。随后的研究表明，miR-20 a直接靶向髓系细胞白血病序列1（Mcl-1），并降低HCC细胞中Mcl-1的内源性蛋白水平。miR-20 a在HCC中降低，并与HCC复发和预后相关。下调miR-20 a可增强HCC细胞的增殖能力。我们的研究结果表明，miR-20 a可能代表一种新的潜在治疗靶点和HCC患者生存的生物标志物。
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.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
3.8
作者：
Schulze-Bergkamen H;Fleischer B;Schuchmann M;Weber A;Weinmann A;Krammer PH;Galle PR
通讯作者：
Galle PR
MicroRNA-20a过表达抑制胰腺癌细胞增殖和转移
影响因子：
4.2
作者：
Yan, Haijiao;Wu, Jiangxue;Huang, Wenlin
通讯作者：
Huang, Wenlin
影响因子：
120.7
作者：
Schetter, Aaron J.;Leung, Suet Yi;Harris, Curtis C.
通讯作者：
Harris, Curtis C.
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM