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

Pan,Yancheng; Sun,Ying; Liu,Ziqi; Zhang,Chao

doi:10.3892/mmr.2020.11213

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

Authors:
- Yancheng Pan
- Ying Sun
- Ziqi Liu
- Chao Zhang
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Affiliations: Department of Pharmacy, The Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Department of Pharmacy, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264000, P.R. China
Published online on: June 4, 2020 https://doi.org/10.3892/mmr.2020.11213
Pages: 1594-1604

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Abstract

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, β‑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 β‑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/β‑catenin signaling pathway.

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