miR-218 suppressed the growth of lung carcinoma by reducing MEF2D expression.

Lung carcinoma is a deadly malignant disease with poor prognosis and increasing incidence in recent years. However, the molecular mechanism underlying the initiation and progression of lung cancer is still not completely elucidated. Recently, myocyte enhancer factor 2D (MEF2D) has been reported to promote the growth of liver cancer, but its implication in lung cancer is still unknown. This study is aimed to determine the role of MEF2D in lung carcinoma. Quantitative PCR (qPCR) and immunoblot assays showed that MEF2D was overexpressed in lung cancer tissues and cell lines, compared with the matched normal tissues and cell lines. Small interfering RNA (siRNA) suppression of MEF2D was able to reduce the proliferation, survival, and invasion of lung carcinoma cells. The transfection of MEF2D-expressing constructs into normal lung fibroblast cells promoted their proliferation and motility. The role of MEF2D in the growth of lung cancer was also confirmed in mice. Further study revealed that miR-218, which was underexpressed in lung carcinoma, was predicted to bind the 3'-untranslated region (UTR) of MEF2D mRNA. miR-218 was shown to suppress the activity of luciferase with MEF2D 3'-UTR. The changes in miR-218 levels affected the expression of MEF2D in lung cancer cells and normal fibroblast cells. There is also an inverse association between miR-218 abundance and MEF2D levels in the lung carcinoma specimen. Furthermore, the transfection of a plasmid that expressed MEF2D resistance to miR-218 regulation abolished the inhibitory effect of miR-218 on lung cancer cells. Collectively, MEF2D overexpression participated in the growth of lung cancers and its aberrant expression may result from the reduction of tumor suppressor miR-218.