TWIST1 upregulates miR-214 to promote epithelial-to-mesenchymal transition and metastasis in lung adenocarcinoma
TWIST1 upregulates miR-214 to promote epithelial-to-mesenchymal transition and metastasis in lung adenocarcinoma
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TWIST1上调miR-214促进肺腺癌上皮间质转化和转移
DOI：
10.3892/ijmm.2018.3630
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发表时间：
2018-07-01
影响因子：
5.4
通讯作者：
Zhu, Bo
中科院分区：
文献类型：
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作者：
Liu, Chao;Luo, Jing;Zhu, Bo
上皮细胞向间质细胞转化（EMT）是非侵袭性肿瘤细胞向恶性转化和转移的关键。我们发现miR-214在肺腺癌（LAD）中表达增加，并与EMT介导的转移呈正相关。然而，microRNAs（miRNAs），如miR-214的过表达，促进LAD中EMT的机制仍不清楚。在这项研究中，我们发现，TWIST 1，一个独立的预后因素，总生存率，增加了左前降支，并与左前降支复发和进展呈正相关。我们还发现TWIST 1参与了LAD细胞的EMT过程和转移。最重要的是，在临床LAD组织中发现miR-214和TWIST 1的表达之间呈正相关。此外，miR-214表达下降，其靶基因融合同源物抑制因子（SUFU）在LAD细胞中增加，以响应通过shRNA抑制TWIST 1表达。总之，本研究首次提供证据表明TWIST 1的高表达增加了miR-214的表达，从而促进了LAD的EMT过程和转移。这些发现有助于阐明miRNAs调控EMT过程的机制，并提示一条新的TWIST 1-miR-214通路参与了LAD的迁移和侵袭。
Epithelial-to-mesenchymal transition (EMT) is essential for the progression of non-invasive tumor cells into malignancy and metastasis. We found that miR-214 was increased in lung adenocarcinoma (LAD) and positively associated with metastasis, which was mediated by EMT. However, the mechanism whereby the overexpression of microRNAs (miRNAs), such as miR-214, promote EMT in LAD remains unclear. In this study, we found that TWIST1, an independent prognostic factor for overall survival, was increased in LAD and correlated positively with LAD recurrence and progression. We also found that TWIST1 contributes to the EMT process and metastasis of LAD cells. Most importantly, a positive correlation was found between the expression of miR-214 and TWIST1 in clinical LAD tissue. Additionally, miR-214 expression was decreased and its target gene suppressor of fused homolog (SUFU) was increased in LAD cells in response to the impairment of TWIST1 expression by shRNA. Overall, this study provides the first evidence to show that the high expression of TWIST1 increases the expression of miR-214 to promote the EMT process and metastasis in LAD. These findings contribute to clarify the mechanisms whereby miRNAs regulate the EMT process and implicate a new TWIST1-miR-214 pathway in the control of migration and invasion of LAD.