MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in hepatocellular carcinoma.
MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in hepatocellular carcinoma.
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MicroRNA-503 通过下调肝细胞癌中的细胞周期蛋白 D3 和 E2F3 来抑制 G1/S 转变。
DOI：
10.1186/1479-5876-11-195
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发表时间：
2013-08-22
影响因子：
7.4
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Xiao F;Zhang W;Chen L;Chen F;Xie H;Xing C;Yu X;Ding S;Chen K;Guo H;Cheng J;Zheng S;Zhou L
越来越多的证据表明，microRNAs(MiRNAs)的去调控参与了肿瘤的发生。在包括癌症在内的各种疾病中都观察到了microRNA-503的下调。然而，miR-503在肝细胞癌中的生物学功能仍很不清楚。在本研究中，我们旨在阐明miR-503在肝细胞癌中的预后意义及其病理生理作用。用定量逆转录聚合酶链式反应检测miR-503在肝细胞癌组织和细胞系中的表达。Western blotting检测miR-503靶基因的表达。通过体内和体外实验评价miR-503在肝癌中的作用。用荧光素酶报告基因分析验证miR-503靶基因。MIR-503在肝癌细胞系和组织中经常下调。MiR-503低表达与门静脉癌栓、组织学分级、TNM分期、AFP水平及预后不良等恶性潜能增强相关。多因素分析显示miR-503基因表达下调与肝细胞癌患者的总体生存率显著相关。功能研究表明，miR-503通过Rb-E2F信号通路诱导细胞周期停滞于G1期，从而抑制肝癌细胞的增殖，从而可能作为肿瘤抑制因子发挥作用。进一步的研究确定了两个与细胞周期相关的分子，细胞周期蛋白D3和E2F3，作为miR-503的直接靶标。我们的研究结果突出了miR-503在细胞周期调控和肝癌分子病因学中的重要作用，并暗示miR-503在预后预测和基于miRNA的肝癌治疗中具有潜在的应用价值。
Increasing evidence indicates that deregulation of microRNAs (miRNAs) is involved in tumorigenesis. Downregulation of microRNA-503 has been observed in various types of diseases, including cancer. However, the biological function of miR-503 in hepatocellular carcinoma (HCC) is still largely unknown. In this study we aimed to elucidate the prognostic implications of miR-503 in HCC and its pathophysiologic role. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate miR-503 expression in HCC tissues and cell lines. Western blotting was performed to evaluate the expression of the miR-503 target genes. In vivo and in vitro assays were performed to evaluate the function of miR-503 in HCC. Luciferase reporter assay was employed to validate the miR-503 target genes. miR-503 was frequently downregulated in HCC cell lines and tissues. Low expression levels of miR-503 were associated with enhanced malignant potential such as portal vein tumor thrombi, histologic grade, TNM stage, AFP level and poor prognosis. Multivariate analysis indicated that miR-503 downregulation was significantly associated with worse overall survival of HCC patients. Functional studies showed miR-503 suppressed the proliferation of HCC cells by induction of G1 phase arrest through Rb-E2F signaling pathways, and thus may function as a tumor suppressor. Further investigation characterized two cell cycle-related molecules, cyclin D3 and E2F3, as the direct miR-503 targets. Our data highlight an important role for miR-503 in cell cycle regulation and in the molecular etiology of HCC, and implicate the potential application of miR-503 in prognosis prediction and miRNA-based HCC therapy.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
3.8
作者：
Jiang Q;Feng MG;Mo YY
通讯作者：
Mo YY
miR-16 家族通过调节多个细胞周期基因诱导细胞周期停滞。
影响因子：
14.9
作者：
Liu Q;Fu H;Sun F;Zhang H;Tie Y;Zhu J;Xing R;Sun Z;Zheng X
通讯作者：
Zheng X
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P