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.

The miR-199a/214 Cluster Controls Nephrogenesis and Vascularization in a Human Embryonic Stem Cell Model

“…These branched CDH1 + tubules in 2D cultures are more likely to represent ureteric bud derivatives and inhibiting miR-214-3p could, thus, favor ureteric bud epithelium stabilization, while restricting MM (as shown by the reduction in WT1 + cells). In agreement with this interpretation, CDH1 itself has been previously reported as a direct target of miR-214 (Wang et al, 2016), while in some cancers miR-214 was found to promote EMT (Liu et al, 2018a;Long et al, 2015;Zhao et al, 2018) and therefore inhibiting it would be expected to result in epithelial stabilization.…”

MicroRNA-214 Prevents Pulmonary Angiogenesis and Alveolarization in Rat Models with Bronchopulmonary Dysplasia via PlGF-Dependent STAT3 Signaling Pathway

“…MiR-214, a member of microRNA precursors, plays a pivotal role in the pathogenesis of multiple human disorders, including cardiovascular diseases and cancers [24,25]. The expression of miR-214 increased by TWIST1 promotes the epithelial-to-mesenchymal transition and metastasis in lung adenocarcinoma [26]. Additionally, our study portrayed that PlGF, which was highly expressed in the lung tissues of preterm rats with BPD, was negatively targeted by miR-214 and activated the STAT3 signaling pathway.…”

MicroRNA-214 prevents pulmonary angiogenesis and alveolarization in neonatal rats with hyperoxia-mediated impairment of lung development by blocking PlGF-dependent STAT3 signaling pathway

“…7D-E). These results lung adenocarcinoma (16). Additionally, our study portrayed that PlGF, which was highly expressed 399 in the lung tissues of preterm rats with BPD, was negatively targeted by miR-214 and activated the 400 STAT3 signaling pathway.…”

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In recent years, the roles of microRNAs (miRNAs) in pulmonary diseases have been 16 widely studied and researched. However, the molecular mechanism by which miR-214 affects 17 bronchopulmonary dysplasia (BPD) remains elusive and merits further exploration.

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