miR-1470 Mediates Lapatinib Induced p27 Upregulation by Targeting c-jun
miR-1470 Mediates Lapatinib Induced p27 Upregulation by Targeting c-jun
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miR-1470 通过靶向 c-jun 介导拉帕替尼诱导的 p27 上调
DOI：
10.1002/jcp.24910
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发表时间：
2015-07-01
影响因子：
5.6
通讯作者：
Guan, Xiaoxiang
中科院分区：
文献类型：
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作者：
Nie, Weiwei;Song, Wei;Guan, Xiaoxiang
我们先前的研究表明，拉帕替尼通过转录和翻译后机制诱导p27依赖的G(1)期停滞。利用miRNA芯片技术和定量RT-PCR技术，我们进一步研究了雷帕替尼作用下p27上调和HER-2信号通路改变的潜在miRNAs。0.5 mU M和2.0 mU M以及24小时和48小时的拉帕替尼处理均显著影响了7个miRNAs的亚群。经KEGG通路分析，HER-2通路中仅鉴定出miR-1470、miR-126和miR-1208。然而，荧光素酶报告实验证实miR-1470直接识别c-jun转录本的3-非翻译区，这与TargetScan分析一致。MiR-1470可显著降低c-jun的表达，从而抑制c-jun对细胞周期蛋白1表达的激活，从而促进细胞周期停滞的关键分子p27的表达上调。综上所述，本研究首次提供了miR-1470介导的拉帕替尼通过靶向c-jun而诱导p27上调的证据。J.细胞。物理。230：1630-1639,2015。(C)2014年威利期刊公司，A Wiley Company
Our previous study indicated that lapatinib induces p27-dependent G(1) arrest through both transcriptional and post-translational mechanisms. Using miRNA microarray technology and quantitative RT-PCR, we further investigated the potential miRNAs that involved in p27 upregulation and Her-2 signaling pathway alteration with lapatinib treatment. A subset of 7 miRNAs was significantly affected in both 0.5 mu M and 2.0 mu M and 24h and 48h lapatinib treatment. Among them, only miR-1470, miR-126, and miR-1208 were identified in the Her-2 pathway after KEGG pathway analysis. However, luciferase reporter assay confirmed that miR-1470 directly recognized the 3-untranslated region of c-jun transcripts, which was consistent with TargetScan analysis. miR-1470 significantly decreased c-jun expression, thus miR-1470 may repressc-jun activation of cyclinD1 expression, and consequently promoted the upregulation of p27, a key molecule in the cell cycle arrest. Taken together, the present study provided the first evidences that miR-1470 mediated lapatinib induced p27 upregulation by targeting c-jun. J. Cell. Physiol. 230: 1630-1639, 2015. (c) 2014 Wiley Periodicals, Inc., A Wiley Company