MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma.

MicroRNA-182 downregulates metastasis suppressor 1 and contributes to metastasis of hepatocellular carcinoma.
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MicroRNA-182 下调转移抑制因子 1,促进肝细胞癌的转移。

DOI:
10.1186/1471-2407-12-227
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发表时间:
2012-06-08
期刊:
影响因子:
3.8
通讯作者:
Zhang X
Zhang X
中科院分区:
医学2区
文献类型:
--
作者:
Wang J;Li J;Shen J;Wang C;Yang L;Zhang X

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MiR-182是肝细胞癌中表达上调最显著的miRNAs之一。转移抑制基因1(MTSS1)是miR-182的靶基因之一,在肿瘤转移中起重要作用。然而,miR-182和MTSS1在肝细胞癌中的作用和机制尚不清楚。应用实时荧光定量聚合酶链式反应技术检测86例配对的肝癌组织和正常肝组织中miR-182的表达,并分析miR-182的表达与临床病理参数的关系。用免疫组织化学和免疫印迹法检测MTSS1在上述组织中的表达,并分析其与miR-182表达的相关性。此外,将前miR-182或抗miR-182分别导入肝癌细胞系,进行Western印迹和侵袭实验。此外,荧光素酶检测证实miR-182对MTSS1的调节作用。与正常肝组织相比,肝癌组织中miR-182表达上调,MTSS1表达下调。此外,miR182的过度表达与肝内转移(p = 0.034)和预后不良(p = 0.039)有关。在肝癌组织(r = −0.673,p < )和肝癌细胞系(r = −0.931,p = 0.021)中,miR182和mTSS1的表达均呈负相关。此外,miR-182表达上调导致MTSS1表达下调,HUN-1侵袭能力增强,抑制miR-182表达也证实了相反的结果。此外,荧光素酶检测结果表明miR-182对MTSS1具有靶向调控作用。MIR-182可促进肝癌的转移,抑制MTSS1的表达。MIR-182和MTSS1是肝细胞癌潜在的预后标志物和/或治疗靶点。
miR-182 is one of the most significantly up-regulated miRNAs in hepatocellular carcinoma (HCC). Metastasis suppressor 1 (MTSS1), one target gene of miR-182, plays an important role in the metastasis of cancers. However, it remains unclear what role does function and mechanism of miR-182 and MTSS1play in HCC. miR-182 expression was tested in 86 cases of paired HCC and normal tissues by real-time PCR and the relationships between miR-182 expression and clinicopathological parameters were analyzed. The expression of MTSS1 was evaluated by immunohistochemistry and western blot in the above tissues and its correlation with miR-182 expression was analyzed. Moreover, western blot and invasion assays were performed after transfection of pre-miR-182 or anti-miR-182 to HCC cell lines. In addition, luciferase assays was performed to confirm the regulation of miR-182 on MTSS1. Compared with normal tissue, miR-182 was up-regulated and MTSS1 was down-regulated in HCC tissues. Moreover, the over-expression of miR-182 was correlated with intrahepatic metastasis (p = 0.034) and poor prognosis (p = 0.039) of HCC patients. There was a negative correlation between miR-182 and MTSS1 expression in both HCC tissues (r = −0.673, p < 0.01) and HCC cell lines (r = −0.931, p = 0.021). Furthermore, the up-regulation of miR-182 resulted in the down-regulation of MTSS1 and increased invasive potential of HUH-1, and reverse results were also confirmed when the expression of miR-182 was inhibited. In addition, the results of the luciferase assay demonstrated the targeted regulation of miR-182 on MTSS1. miR-182 could promote metastasis of HCC and inhibit the expression of MTSS1. miR-182 and MTSS1 are potential prognostic markers and/or therapeutic targets in HCC.
DOI: 10.1158/0008-5472.can-10-3647
发表时间: 2011-05-15
期刊: CANCER RESEARCH
影响因子: 11.2
作者:
Dai, Bingbing;Meng, Jieru;Roth, Jack A.
通讯作者: Roth, Jack A.
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发表时间: 2009-02-10
影响因子: 11.1
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通讯作者: Hernando, Eva
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发表时间: 2011-04-15
期刊: CANCER RESEARCH
影响因子: 11.2
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DOI: 10.1016/j.canlet.2004.05.002
发表时间: 2004-11-25
期刊: CANCER LETTERS
影响因子: 9.7
作者:
Nixdorf, S;Grimm, MO;Jackson, P
通讯作者: Jackson, P
DOI: 10.1042/bj20021962
发表时间: 2003-04-15
影响因子: 4.1
作者:
Woodings, JA;Sharp, SJ;Machesky, LM
通讯作者: Machesky, LM