Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells.
Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells.
复制标题
通过在甲状腺癌细胞中转录后上调 ZEB1 来敲低 Beclin 1 来诱导上皮间质转化 (EMT)
DOI：
10.18632/oncotarget.12217
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发表时间：
2016-10-25
期刊：
影响因子：
--
通讯作者：
Wang HQ
中科院分区：
文献类型：
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作者：
Li S;Zhang HY;Du ZX;Li C;An MX;Zong ZH;Liu BQ;Wang HQ
Beclin-1是一种单倍体缺陷的肿瘤抑制基因，存在于多种人类肿瘤中。为了阐明Beclin 1在甲状腺癌中的作用，我们在甲状腺癌细胞系中对Beclin 1进行了基因敲除。目前的研究表明，Beclin 1基因敲除导致甲状腺癌细胞发生与上皮-间充质转化(EMT)一致的形态和分子变化，在EMT的形态发生过程中，细胞失去上皮特征，获得间质特征，同时伴随着基因表达重新编程。此外，本研究提供的证据表明，Beclin 1基因敲除通过上调AU结合因子1(AUF1)来稳定EMT诱导物ZEB1mRNA，从而触发了这一转移过程。AUF1被招募到ZEB1mRNA的3‘-非翻译区(UTR)，并减少其降解。在甲状腺癌组织中，Beclin 1与AUF1、ZEB1呈负相关。这些结果表明，在甲状腺癌中，Beclin 1的部分抑瘤作用是通过AUF1对ZEB1的转录后调控而实现的。
Beclin 1 has emerged as a haploinsufficient tumor suppression gene in a variety of human carcinomas. In order to clarify the role of Beclin 1 in thyroid cancer, Beclin 1 was knockdown in thyroid cancer cell lines. The current study demonstrated that knockdown of Beclin 1 resulted in morphological and molecular changes of thyroid cancer cells consistent with epithelial-mesenchymal transition (EMT), a morphogenetic procedure during which cells lose their epithelial characteristics and acquire mesenchymal properties concomitantly with gene expression reprogramming. In addition, the current study presented evidence demonstrating that Beclin 1 knockdown triggered this prometastatic process via stabilization of the EMT inducer ZEB1 mRNA through upregulation of AU-binding factor 1 (AUF1), which is recruited to the 3′-untranslated region (UTR) of the ZEB1 mRNA and decreases its degradation. We also found a negative correlation of Beclin 1 with AUF1 or ZEB1 in thyroid cancer tissues. These results indicated that at least some tumor suppressor functions of Beclin 1 were mediated through posttranscriptional regulation of ZEB1 via AUF1 in thyroid cancers.