Down-Regulated MAC30 Suppresses Lung Cancer Invasion and EMT by Inhibiting Wnt/β-Catenin Signaling Pathway

Abstract Backgrounds：Over-expressed meningioma-associated protein (MAC30) was proved to be a biomarker for worse prognosis in non–small cell lung cancer (NSCLC). However, the regulated mechanism of MAC30 in epithelial–mesenchymal transition (EMT) and lung cancer invasion is unknown. Methods：Transformed growth factor (TGF-β) was used to induce EMT in A549 cells in vitro. MAC30 siRNA was transfected into cells to silence the gene expression. Real-Time PCR was prepared to assess the levels of MAC30 mRNA. Methyl thiazolyl tetrazolium (MTT) and Transwell invasion assays were performed to study the proliferation and invasion of A549 cells. Expression of MAC30, EMT-related proteins, Wnt/β-catenin signal and its downstream factors were explored by ELISA. Results: We found enhanced MAC30 expression in A549 cells. MAC30 Knockdown inhibited TGF-β-induced lung cell proliferation and invasion. Furthermore, elevated levels of mesenchymal markers (N-cadherin, vimentin) and decreased levels of epithelial markers E-cadherin in A549 cells with TGF-β incubation were reversed by MAC30 siRNA. Finally, MAC30 knockdown significantly suppressed TGF-β-upregulated protein levels of Wnt/ β-catenin signaling and its downstream genes (surviving, c-myc and cyclin D1). Conclusions: We firstly confirm that MAC30 knockdown limits lung cancer growth and EMT through inhibiting the activation of Wnt/β-catenin pathway.