Transcription factor c-Myb promotes the invasion of hepatocellular carcinoma cells via increasing osteopontin expression.
Transcription factor c-Myb promotes the invasion of hepatocellular carcinoma cells via increasing osteopontin expression.
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DOI：
10.1186/1756-9966-29-172
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发表时间：
2010-12-30
期刊：
影响因子：
--
通讯作者：
Ye SL
中科院分区：
文献类型：
--
作者：
Chen RX;Xia YH;Xue TC;Ye SL
特定基因的表达受到多种转录因子的严格调控。骨桥蛋白(OPN)是一种磷酸化蛋白，可介导肝细胞癌的进展和转移。然而，OPN在肝细胞癌转移中上调的机制尚不清楚。应用基于寡核苷酸阵列的转录因子检测方法，比较了两种不同OPN表达水平的人肝癌细胞系中转录因子的活性差异。进一步评价一种转录因子对骨桥蛋白表达的影响。11个转录因子在转移性肝癌细胞系HCCLM6中高表达，12个转录因子下调。凝胶迁移率改变分析(EMSA)和报告基因分析表明，上调的转录因子c-Myb可以结合OPN启动子并提高其转录活性。此外，针对c-Myb的小干扰RNA可以抑制OPN的表达，并显著降低HCCLM6细胞的体外迁移和侵袭能力。我们的研究首次证明c-Myb在肝细胞癌OPN表达调控中具有重要的功能，提示c-Myb可能成为控制肝细胞癌转移的新靶点。
Specific gene expression is tightly regulated by various transcription factors. Osteopontin (OPN) is a phosphoprotein that mediates hepatocellular carcinoma (HCC) progression and metastasis. However, the mechanism of OPN up-regulation in HCC metastasis remains to be clarified. Oligonucleotide array-based transcription factor assays were applied to compare different activities of transcription factors in two human HCC cell lines with different OPN expression levels. The effects of one selected transcription factor on OPN expression were further evaluated. Eleven transcription factors were over-expressed in metastatic HCC cell line HCCLM6 cells whereas twelve transcription factors were down-regulated. Electrophoretic mobility shift assays (EMSA) and reporter gene assays showed that one of up-regulated transcription factors c-Myb could bind the OPN promoter and increase its transcription activity. In addition, small interfering RNA targeting c-Myb could inhibit OPN expression and significantly decrease migration and invasion of HCCLM6 cells in vitro. Our data first demonstrate that c-Myb has a functionally important role in the regulation of OPN expression in HCC cells, suggesting that c-Myb might be a new target to control HCC metastasis.
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影响因子：
4.1
作者：
HIJIYA, N;SETOGUCHI, M;YAMAMOTO, S
通讯作者：
YAMAMOTO, S
DOI：
10.1073/pnas.0800970105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Ali, Syed A.;Zaidi, Sayyed K.;Stein, Janet L.
通讯作者：
Stein, Janet L.
影响因子：
11.5
作者：
Coppola, D;Szabo, M;Yeatman, TJ
通讯作者：
Yeatman, TJ
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
4.8
作者：
Fang, Feng;Rycyzyn, Michael A.;Clevenger, Charles V.
通讯作者：
Clevenger, Charles V.