LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer.
LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer.
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DOI：
10.18632/oncotarget.3457
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Bai XZ
中科院分区：
文献类型：
--
作者：
Shi SJ;Wang LJ;Yu B;Li YH;Jin Y;Bai XZ
曲妥珠单抗耐药是her2阳性乳腺癌患者死亡的主要原因，TGF-β诱导的上皮-间质转化（EMT）在曲妥珠单抗耐药中的作用已得到证实，但lncrna在曲妥珠单抗耐药中的作用尚不清楚。在这里，我们产生了曲妥珠单抗耐药的乳腺癌细胞，与亲本细胞相比，其侵袭性增加，并观察到这些细胞中强劲的上皮-间质转化（EMT）和持续升高的TGF-β信号传导。我们发现TGF-β激活的长链非编码RNA （lnc-ATB）是TR SKBR-3细胞和TR乳腺癌患者组织中最显著上调的lncRNA。我们发现lnc-ATB通过竞争性抑制miR-200c，上调ZEB1和ZNF-217，进而诱导EMT，从而促进乳腺癌的曲妥珠单抗耐药和侵袭转移级联。此外，我们还发现lnc-ATB高水平与乳腺癌患者曲妥珠单抗耐药相关。因此，这些研究结果表明，lncRNA-ATB作为TGF-β信号传导的介质，可能使乳腺癌患者易发生EMT和曲妥珠单抗耐药。
Trastuzumab resistance is leading cause of mortality in HER2-positive breast cancers, and the role of TGF-β-induced epithelial-mesenchymal transition (EMT) in trastuzumab resistance is well established, but the involvement of lncRNAs in trastuzumab resistance is still unknown. Here, we generated trastuzumab-resistant breast cancer cells with increased invasiveness compared with parental cells, and observed robust epithelial–mesenchymal transition (EMT) and consistently elevated TGF-β signaling in these cells. We identified long noncoding RNA activated by TGF-β (lnc-ATB) was the most remarkably upregulated lncRNA in TR SKBR-3 cells and the tissues of TR breast cancer patients. We found that lnc-ATB could promote trastuzumab resistance and invasion-metastasis cascade in breast cancer by competitively biding miR-200c, up-regulating ZEB1 and ZNF-217, and then inducing EMT. In addition, we also found that the high level of lnc-ATB was correlated with trastuzumab resistance of breast cancer patients. Thus, these findings suggest that lncRNA-ATB, a mediator of TGF-β signaling, could predispose breast cancer patients to EMT and trastuzumab resistance.
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影响因子：
3.5
作者：
Hilmarsdottir B;Briem E;Bergthorsson JT;Magnusson MK;Gudjonsson T
通讯作者：
Gudjonsson T
影响因子：
--
作者：
Su X;Malouf GG;Chen Y;Zhang J;Yao H;Valero V;Weinstein JN;Spano JP;Meric-Bernstam F;Khayat D;Esteva FJ
通讯作者：
Esteva FJ
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1073/pnas.0308090100
发表时间：
2004-02-03
影响因子：
11.1
作者：
Seton-Rogers, SE;Lu, Y;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
45.3
作者：
Niikura, Naoki;Liu, Jun;Ueno, Naoto T.
通讯作者：
Ueno, Naoto T.