TGF-β1-induced epithelial-mesenchymal transition in lung cancer cells involves upregulation of miR-9 and downregulation of its target, E-cadherin

• Published in: Cellular & molecular biology letters Vol. 22; no. 1; pp. 22 - 10
• Main Authors: Wang, Hui, Wu, Qian, Zhang, Ying, Zhang, Hua-Nan, Wang, Yong-Bin, Wang, Wei
• Format: Journal Article
• Language: English
• Published: England BioMed Central 02.11.2017; BMC
• Subjects: Base Sequence; Biotechnology; Cadherins - genetics; Cadherins - metabolism; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cells; Down-Regulation - drug effects; E-cadherin; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic - drug effects; Genotype & phenotype; HEK293 Cells; Humans; Invasion; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical prognosis; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; MiR-9; Non-small cell lung carcinoma; NSCLC; Proteins; Small cell lung carcinoma; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; Up-regulation; Up-Regulation - drug effects; NSCLC; MiR-9; E-cadherin; Invasion
• ISSN: 1425-8153; 1689-1392
• DOI: 10.1186/s11658-017-0053-1

TGF-β1 plays an important role in the epithelial-mesenchymal transition (EMT) of epithelial cancers, including non-small cell lung cancer (NSCLC). While the full underlying mechanism remains unclear, miR-9 is known to play a critical role in the regulation of NSCLC cell invasion. We tested whether miR-9 targets E-cadherin and thus affects TGF-β1-induced EMT in NSCLC cells by assessing the expression levels of miR-9 and E-cadherin for NSCLC patients and then verifying the targeting of E-cadherin by miR-9 using the dual luciferase reporter system. MiR-9 was significantly upregulated in NSCLC tissues compared with its level in adjacent normal tissues. The expression of E-cadherin in NSCLC tissues was significantly decreased. In addition, we found that TGF-β1 significantly upregulated the expression of miR-9 and downregulated the expression of E-cadherin. E-cadherin was confirmed as a direct target gene of miR-9. Using an miR-9 inhibitor reversed the TGF-β1-mediated inhibition of E-cadherin expression and upregulation of the mesenchymal marker α-SMA. TGF-β1 significantly induced cell invasion, and this effect was significantly inhibited by miR-9 inhibitors. TGF-β1 induced EMT in NSCLC cells by upregulating miR-9 and downregulating miR-9's target, E-cadherin.