Objective: The ERK/MAPK signaling pathway regulates cell proliferation and invasion. MAPK kinase 1 (MEK1) is a protein kinase upstream of ERK that can activate the pathway. Expression of microRNA (miR)-16 in lung cancer tissues is decreased. The aim of this study was to determine roles of miR-16 in proliferation and invasion of lung cancer cells.
Methods: We used a luciferase reporter assay to determine a regulatory relationship between miR-16 and MEK1 and assessed expression of MEK1 in normal lung cells and lung cancer cell lines. Plate cloning, flow cytometry, and Transwell experiments demonstrated the proliferation and invasion ability of cells transfected with wild-type and mutant MEK1.
Results: We confirmed a regulatory relationship between miR-16 and MEK1 mRNA. Expression of miR-16 was decreased and that of MEK1 and p-ERK1/2 were increased in lung cancer cell lines compared with normal cells. Transfection with miR-101 mimic or small interfering (si)-MEK1 significantly downregulated expression of MEK1 and p-ERK1/2 in Anip973 cells.
Conclusions: Decreased miR-16 expression may play a role in upregulating expression of MEK1 and promoting proliferation and invasion of lung cancer cells. Overexpression of miR-16 downregulated the ERK/MAPK pathway by inhibiting MEK1 expression, attenuating clone formation and invasion, and inhibiting cell proliferation.
Keywords: ERK/MAPK; MAPK kinase 1; MEK1; MicroRNA-16; invasion; lung cancer; miR-16; proliferation.