miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells
miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells
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DOI：
10.1016/j.canlet.2008.09.035
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发表时间：
2009-03-08
期刊：
影响因子：
9.7
通讯作者：
Zheng, Xiaofei
中科院分区：
文献类型：
--
作者：
Li, Na;Fu, Hanjiang;Zheng, Xiaofei
一些研究表明，miR-34a抑制许多基因的表达，并诱导G1期停滞、细胞凋亡和衰老。在本研究中，我们确定了miR-34a在调节肿瘤细胞的散射、迁移和侵袭中的作用。在25例人肝细胞癌组织中，有19例(76%)miR-34a表达下调，与癌旁正常组织相比有高度显著性差异，并与肿瘤的转移和侵袭有关。此外，25例肝癌切除的正常组织/肿瘤组织中miR-34a与c-Met-蛋白的表达呈负相关。在HepG2细胞中，miR-34a的异位表达以c-Met依赖的方式有效地抑制肿瘤细胞的迁移和侵袭。MIR-34a直接靶向c-Met，降低c-Met的mRNA和蛋白水平，从而抑制c-Met诱导的细胞外信号调节激酶1和2(ERK1/2)的磷酸化。综上所述，这些结果为miR-34a通过调节c-Met信号通路在肿瘤侵袭转移中的抑制作用提供了证据。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Several studies have shown that miR-34a represses the expression of many genes and induces G1 arrest, apoptosis, and senescence. In the present study, we identified the role of miR-34a in the regulation of tumor cell scattering, migration, and invasion. Down-regulation of miR-34a expression was highly significant in 19 of 25 (76%) human hepatocellular carcinoma (HCC) tissues compared with adjacent normal tissues and associated with the metastasis and invasion of tumors. Furthermore, resected normal/tumor tissues of 25 HCC patients demonstrated an inverse correlation between miR-34a and c-Met-protein. In HepG2 cells, ectopic expression of miR-34a potently inhibited tumor cell migration and invasion in a c-Met-dependent manner. miR-34a directly targeted c-Met and reduced both mRNA and protein levels of c-Met; thus, decreased c-Met-induced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Taken together, these results provide evidence to show the suppression role of miR-34a in tumor migration and invasion through modulation of the c-Met signaling pathway. (C) 2008 Elsevier Ireland Ltd. All rights reserved.