TWIST1 upregulates miR-214 to promote epithelial-to-mesenchymal transition and metastasis in lung adenocarcinoma

Abstract

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.