Lung carcinoma greatly threatens human health, due to its increasing incidence in recent years and poor prognosis. However, this malignancy displays resistance against current therapeutic strategies. One of major causes leading to bad outcomes for lung cancer therapy is the lack of understanding on its tumorigenesis and progression. To explore the molecular mechanism by which lung cancer progresses, we employed multidisciplinary approaches and used lung cancer cell lines as research models. miR-1244 was underexpressed in lung carcinoma by 40.6-73.8%, which is highly associated with patients' survival. miR-1244 restoration was shown to affect the proliferation, survival, and invasion of lung cancer cells. miR-1244 suppression rendered normal lung fibroblasts with malignant phenotypes. miR-1244 overexpression can reduce the growth of lung cancer xenografts. miR-1244 was then verified to negatively regulate the expression of myocyte enhancer factor 2D (MEF2D) in lung cancer cells. MEF2D can also affect the expression of miR-1244 by directly binding to its promoter. Further study showed that MEF2D is required for the effect of miR-1244 on lung cancer and normal cells. These results suggested that there is an autoregulatory circuit consisting of miR-1244 and MEF2D, which contributes to the progression of lung cancer. Targeting this molecular loop may be a promising strategy for lung carcinoma treatment.