Silencing of miR-1247 by DNA methylation promoted non-small-cell lung cancer cell invasion and migration by effects of STMNI

Abstract

MicroRNAs (miRNAs) play an important role in cancer development and progression, altering several biological functions by affecting targets through either degradation of mRNAs or suppression of protein translation. One such miRNA, miR-1247, is downregulated in various cancers, but its biological role in non-small-cell lung cancer (NSCLC) is unknown. This study found that the expression of miR-1247 was significantly reduced in NSCLC cell lines and tumor tissues compared with matched normal lung tissues and cell lines as a result of DNA hypermethylation. Overexpression of miR-1247 or demethylation by 5-azacytidine (5-Aza) treatment dramatically inhibited cell growth, migration, invasion, and cell cycle progression. Furthermore, Stathmin 1 (STMN1) was found to be an immediate and functional target of miR-1247. The expression of STMN1 was significantly increased in NSCLC cell lines but was decreased by 5-Aza treatment. In addition, miR-1247 upregulation partially inhibited STMN1-induced promotion of migration and invasion of A549 and H1299 cells. The results suggest that miR-1247 was silenced by DNA methylation. MiR-1247 and its downstream target gene STMN1 may therefore be a future target for the treatment of NSCLC.