RRC ID 37490
Author Sonoki H, Sato T, Endo S, Matsunaga T, Yamaguchi M, Yamazaki Y, Sugatani J, Ikari A.
Title Quercetin Decreases Claudin-2 Expression Mediated by Up-Regulation of microRNA miR-16 in Lung Adenocarcinoma A549 Cells.
Journal Nutrients
Abstract Claudin-2 is highly expressed in human lung adenocarcinoma tissues and cells. Knockdown of claudin-2 decreases cell proliferation and migration. Claudin-2 may be a novel target for lung adenocarcinoma. However, there are no physiologically active substances of foods which decrease claudin-2 expression. We here found that quercetin, a flavonoid present in fruits and vegetables, time- and concentration-dependently decreases claudin-2 expression in lung adenocarcinoma A549 cells. In the present study, we examined what regulatory mechanism is involved in the decrease in claudin-2 expression by quercetin. Claudin-2 expression was decreased by LY-294002, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, and U0126, a MEK inhibitor. These drugs inhibited the phosphorylation of Akt and ERK1/2, which are downstream targets of PI3-K and MEK, respectively. In contrast, quercetin did not inhibit the phosphorylation. Both LY-294002 and U0126 inhibited promoter activity of claudin-2, but quercetin did not. The stability of claudin-2 mRNA was decreased by quercetin. Quercetin increased the expression of microRNA miR-16. An inhibitor of miR-16 rescued quercetin-induced decrease in the claudin-2 expression. These results suggest that quercetin decreases claudin-2 expression mediated by up-regulation of miR-16 expression and instability of claudin-2 mRNA in lung adenocarcinoma cells.
Volume 7(6)
Pages 4578-92
Published 2015-6-8
DOI 10.3390/nu7064578
PII nu7064578
PMID 26061016
PMC PMC4488803
MeSH Adenocarcinoma Adenocarcinoma of Lung Butadienes / pharmacology Cell Line, Tumor Cell Proliferation Chromones / pharmacology Claudins / genetics Claudins / metabolism* Fruit Gene Expression Regulation, Neoplastic* Humans Lung Neoplasms MicroRNAs / genetics MicroRNAs / metabolism* Morpholines / pharmacology Nitriles / pharmacology Phosphatidylinositol 3-Kinases / antagonists & inhibitors Phosphatidylinositol 3-Kinases / metabolism Phosphorylation Promoter Regions, Genetic Quercetin / pharmacology* RNA, Messenger / genetics RNA, Messenger / metabolism Up-Regulation Vegetables
IF 4.196
Times Cited 10
Human and Animal Cells