miR-192-5p upregulation mediates the suppression of curcumin in human NSCLC cell proliferation, migration and invasion by targeting c-Myc and inactivating the Wnt/β-catenin signaling pathway

Curcumin is a naturally active phenolic compound extracted from the rhizome of the plant Curcuma longa, which has been demonstrated to serve as an anticancer drug in different types of cancer, including non-small-cell lung cancer (NSCLC). Accumulating evidence has suggested that curcumin may exert epigenetic regulatory effects on microRNAs (miRs). Therefore, the present study aimed to investigate the role of miR-192-5p, and the effects of curcumin, in NSCLC, alongside the underlying mechanisms. Human NSCLC cells, A427 and A549, were treated with curcumin, and the expression levels of miR-192-5p and c-Myc were detected using reverse transcription-quantitative PCR and western blotting. Cellular proliferation was analyzed using Cell Counting Kit-8 assays and cell viability was determined using a MTT assay. Additionally, the migratory and invasive abilities of cells were analyzed using Transwell and Matrigel assays, respectively. The binding sites between miR-192-5p and c-Myc were predicted using TargetScanHuman software, and confirmed using a dual-luciferase reporter assay and RNA immunoprecipitation. Finally, the Wnt pathway regulator, beta -catenin, and cyclin D1 expression levels were determined using western blotting. Curcumin treatment inhibited NSCLC cell proliferation, migration, invasion and viability in a dose-dependent manner, in addition to promoting a dose-dependent increase in the expression levels of miR-192-5p and a reduction in c-Myc expression levels. Notably, the genetic knockdown of miR-192-5p blocked the inhibitory effects of curcumin on NSCLC progression and instead promoted NSCLC progression, which was observed to be partially reversed by c-Myc silencing; thus, c-Myc was suggested to be a direct target gene of miR-192-5p as demonstrated by the TargetScanHuman database, dual-lucierase and RIP assay results. In addition, the curcumin-induced decreased expression levels of beta -catenin, cyclin D1 and c-Myc were rescued following the genetic knockdown of miR-192-5p. In conclusion, these findings suggested that the upregulation of miR-192-5p may underlie the inhibitory effects of curcumin on NSCLC cells through targeting c-Myc and inactivating the Wnt/beta -catenin signaling pathway.