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首页> 外文期刊>Cellular Signalling >Upregulation of microRNA-141 suppresses epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF-beta signaling pathway
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Upregulation of microRNA-141 suppresses epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF-beta signaling pathway

机译：MicroRNA-141的上调抑制了通过HoxC6依赖性TGF-Beta信号通路抑制喉癌中的上皮 - 间充质转换和淋巴结转移

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Laryngeal cancer is one of the most malignant cancers among the head and neck malignant tumors. Abnormal expression of microRNAs (miRNAs) contributes to cancer development through regulating proliferation and apoptosis of cancer cells. In this study, we aim to explore the roles of microRNA-141 (miR-141), Homeobox C6 (HOXC6) and TGF-beta signaling pathway in epithelial-mesenchymal transition (EMT) and lymph node metastasis in laryngeal cancer. Initially, we identified differentially expressed genes in laryngeal cancer, among which HOXC6 was identified. Then the target miRNA of HOXC6 was predicted and verified. Next, expression of miR-141, HOXC6, TGF-beta 1, Smad3, Vimentin and Snail in cancer tissues was detected. Then, AMC-HN-8 cells were transfected with miR-141 mimic, miR-141 inhibitor and HOXC6-siRNA to investigate specific role of miR-141, HOXC6 and TGF-beta signaling pathway in laryngeal cancer in vivo and in vitro. Our results showed that HOXC6 was a target gene of miR-141, which was downregulated in laryngeal cancer. Besides, overexpression of miR-141 could downregulate HOXC6 and inhibit the TGF-beta signaling pathway. Upregulation of miR-141 or silencing of HOXC6 can repress EMT, viability, migration and invasion abilities of laryngeal cancer cells. In addition, up-regulation of miR-141 inhibited the tumor growth and lymph node metastasis in vivo. In summary, our findings demonstrated that upregulated miR-141 decreased HOXC6 expression, and inhibited the TGF-beta signaling pathway, EMT and lymph node metastasis in laryngeal cancer, which is of clinical significance in the treatment of laryngeal cancer.
机译：喉癌是头部和颈部恶性肿瘤中最恶性癌症之一。 MicroRNAS（miRNA）的异常表达通过调节癌细胞的增殖和凋亡来导致癌症发育。在这项研究中，我们的目标是探讨MicroRNA-141（MIR-141），Homeobox C6（HoxC6）和TGF-β信号传导途径在喉癌中上皮 - 间充质转换（EMT）和淋巴结转移中的作用。最初，我们鉴定了喉癌中的差异表达基因，其中鉴定了HoxC6。然后预测并验证HOXC6的靶miRNA。接下来，检测MiR-141，HoxC6，TGF-β1，Smad3，Vimentin和蜗牛在癌组织中的表达。然后，用miR-141模拟，miR-141抑制剂和HoxC6-siRNA转染AMC-HN-8细胞，以研究MiR-141，HoxC6和TGF-Beta信号传导途径在体内和体外喉癌中的特定作用。我们的研究结果表明，HOXC6是MIR-141的靶基因，其在喉癌中下调。此外，miR-141的过表达可以下调HOXC6并抑制TGF-β信号通路。 MiR-141的上调或HOXC6的沉默可以压制喉癌细胞的EMT，活力，迁移和侵袭能力。此外，MiR-141的上调抑制了体内肿瘤生长和淋巴结转移。总之，我们的研究结果表明，上调的miR-141降低了HoxC6表达，并抑制了喉癌中的TGF-β信号通路，EMT和淋巴结转移，这在治疗喉癌时具有临床意义。

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