Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
Int J Mol Med. 2018 Jul;42(1):461-470. doi: 10.3892/ijmm.2018.3630. Epub 2018 Apr 17.
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.
上皮-间质转化（EMT）对于非侵袭性肿瘤细胞向恶性肿瘤和转移的进展至关重要。我们发现 miR-214 在肺腺癌（LAD）中增加，并与转移呈正相关，这是由 EMT 介导的。然而，miRNAs（如 miR-214）过度表达促进 LAD 中的 EMT 的机制尚不清楚。在这项研究中，我们发现 TWIST1，一种总生存的独立预后因素，在 LAD 中增加，并与 LAD 复发和进展呈正相关。我们还发现 TWIST1 有助于 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 TWIST1 的表达之间存在正相关。此外，在 LAD 细胞中，TWIST1 表达的减少及其靶基因 fused 同源物抑制物（SUFU）的增加响应于 shRNA 对 TWIST1 表达的损害。总的来说，这项研究首次提供了证据表明 TWIST1 的高表达增加了 miR-214 的表达，从而促进了 LAD 中的 EMT 过程和转移。这些发现有助于阐明 miRNAs 调节 EMT 过程的机制，并暗示 TWIST1-miR-214 途径在控制 LAD 的迁移和侵袭方面的新作用。
