MicroRNA‐520c‐3p functions as a novel tumor suppressor in lung adenocarcinoma

Lung cancer is a malignancy with one of the highest incidence rates, and it is the leading cause of cancer‐related death. To gain further insights into the underlying mechanisms of tumor growth and metastasis, we investigated the role and expression of microRNAs in lung adenocarcinoma (LUAD). We discovered a significantly lower expression level of microRNA‐520c‐3p (miR‐520c‐3p) in LUAD tissues than in nontumor tissues. miR‐520c‐3p is known to regulate multiple biological functions and cellular behaviors. In this study, we show that AKT1 and AKT2 are key direct targets of miR‐520c‐3p, which are required for its biological roles in LUAD. Mechanistically, downregulation of miR‐520c‐3p in LUAD is due to DNA methylation of the miR‐520c‐3p promoter region. Conversely, the activity of the transcription factor Yin Yang 1 (YY1) results in the upregulation of miR‐520c‐3p. Taken together, our results reveal methylation/YY1/miR‐520c‐3p/AKT1/AKT2 as a molecular axis with a potent biological function and highlight miR‐520c‐3p as a novel potent tumor suppressor in LUAD.