TGF-β-induced STAT3 overexpression promotes human head and neck squamous cell carcinoma invasion and metastasis through malat1/miR-30a interactions
TGF-β-induced STAT3 overexpression promotes human head and neck squamous cell carcinoma invasion and metastasis through malat1/miR-30a interactions
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TGF-β诱导的STAT3过表达通过malat1/miR-30a相互作用促进人头颈鳞状细胞癌的侵袭和转移。
DOI：
10.1016/j.canlet.2018.08.009
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Zhou, Xuan
中科院分区：
文献类型：
--
作者：
Wang, Yu;Wu, Chuanqiang;Zhou, Xuan
信号转导子和转录激活子3（STAT 3）信号通路异常是头颈部鳞状细胞癌（HNSCC）侵袭和转移的关键因素。然而，STAT 3过表达和调节HNSCC转移的潜在机制仍不清楚。在目前的研究中，我们证明了上调的TGF-β可以通过STAT 3激活促进上皮-间质转化（EMT）。此外，我们探讨了STAT 3对HNSCC的贡献，特别关注其转录调控及其与长链非编码RNA（IncRNA）转移相关肺腺癌转录本1（malat 1）的相互作用。染色质免疫沉淀（ChIP）和荧光素酶报告基因检测显示，STAT 3可与malatl启动子区结合，转录激活malati表达;然后，malatl与miR-30 a相互作用，诱导EMT，加速HNSCC转移。总之，我们的发现阐明了异常STAT 3激活如何在HNSCC中赋予致癌功能，因此可能为STAT 3作为HNSCC治疗靶点提供理论基础。
Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is a critical factor that drives the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of STAT3 overexpression and regulation of HNSCC metastasis remain unknown. In the current study, we demonstrated that upregulated TGF-beta may promote epithelial-mesenchymal transition (EMT) through STAT3 activation. In addition, we explored the contributions of STAT3 to HNSCC with a specific focus on its transcriptional regulation and its interaction with the long noncoding RNA (IncRNA) metastasis associated lung adenocarcinoma transcript 1 (malat1). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that STAT3 could bind to the malatl promoter region and transcriptionally activate malati expression; then, malatl interacted reciprocally with miR-30a, inducing EMT and accelerating HNSCC metastasis. In summary, our discoveries illuminate how aberrant STAT3 activation confers an oncogenic function in HNSCC and therefore may provide a theoretical foundation for STAT3 as a therapeutic target in HNSCC.