EFEMP2 Suppresses the Invasion of Lung Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition (EMT) and Down-Regulating MMPs

Liang Song,1,* Xiang-Xin Li,2,* Xiang-Yan Liu,1 Zhou Wang,1 Yang Yu,1 Mo Shi,1 Bin Jiang,1 Xiao-Peng He1 1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Peng HeDepartment of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, Shandong Province 250021, People’s Republic of ChinaTel/Fax +86-531-6877-7884Email hexiaopeng7715@126.comBackground: Epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (EFEMP2), also known as fibulin-4, MBP1 and UPH1, is an extracellular matrix protein associated with a variety of tumors. The purpose of this study was to investigate the prognostic value and the function of EFEMP2 in lung cancer.Methods: The mRNA and protein expression of EFEMP2 in lung normal and cancer tissues, lung cancer cell lines (A549, H460, H1299 and H1650) and normal epithelial cell line BEAS-2B were evaluated by immunohistochemistry, RT-qPCR and Western blotting. The Public databases (Oncomine and Kaplan-Meier plotter) were used to investigate the prognostic value of EFEMP2 in lung cancer. RNA interference (RNAi) and overexpression transfection were performed to detect the effects of EFEMP2 up- or down-regulation on lung normal and cancer cell proliferation, invasion and metastasis in vitro and in vivo.Results: EFEMP2 was lowly expressed in lung cancer tissues and cells, and its low expression was associated with malignant phenotype and poor prognosis of lung cancer. The same conclusion had been drawn from the Public databases. EFEMP2 overexpression significantly inhibited the invasion of lung cancer cells, hampered the process of EMT, and decreased the expression and activity of MMP2 and MMP9, while EFEMP2 knockdown remarkably enhanced the invasion of lung cancer cells, promoted EMT, and increased the expression and activity of MMP2 and MMP9.Conclusion: The low expression of EFEMP2 was detected in lung cancer and was positively correlated with the poor prognosis of patients. EFEMP2 was a tumor suppressor gene that inhibited the progress of lung cancer, which suggested a new research objective for the future studies.Keywords: EFEMP2, lung cancer, invasion, metastasis, EMT, MMPs