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Mol Carcinog. 2018 Dec;57(12):1835-1844. doi: 10.1002/mc.22901. Epub 2018 Sep 19.

EGCG inhibits CSC-like properties through targeting miR-485/CD44 axis in A549-cisplatin resistant cells.

Author information

1
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.

Abstract

Non-small cell lung cancer (NSCLC) remains one of the most aggressive tumors with low life expectancy worldwide. The existence of cancer stem cells (CSCs) contributes to the failure of cancer treatment resulted from drug resistance. Altered microRNA expression has been observed in human tumors due to its role in tumor growth, progression, and metastasis. Hence, the aim of our present study was to investigate the effects of miR-485 on the CSC-like traits in NSCLC A549-cisplatin resistant cells and concentrate on the underlying molecular mechanism. It was found that CSC-like phenotypes were much more enriched in A549/cisplatin (A549/CDDP) cells compared to A549-parental cells. In addition, we observed that miR-485 was greatly decreased in A549/CDDP cells and miR-485 overexpression was able to decrease the stemness of A549/DDP cells. Meanwhile, epigallocatechin-3-gallate (EGCG), a green tea polyphenol which has been identified as an effective anticancer compound was able to increase miR-485 expression dose-dependently in A549/CDDP cells. Inhibitors of miR-485 remarkably increased CSC-like phenotypes, which could be reversed by indicated doses of EGCG. Moreover, CD44 was predicted as downstream target of miR-485 and the correlation between them was validated by performing dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Subsequently, in vivo experiments were employed to confirm that EGCG restrained CSC-like characteristics by increasing miR-485 and decreasing CD44 expression. Taken together, it was implied that stemness features and CSC population were suppressed by EGCG-modulated miR-485/CD44 axis in A549/CDDP cells.

KEYWORDS:

A549/CDDP; CD44; EGCG; cancer stem cells; miR-485

PMID:
30182373
DOI:
10.1002/mc.22901
[Indexed for MEDLINE]

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