Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis

Quercetin has potential pharmacological values in various carcinomas including oral squamous cell carcinoma (OSCC). Moreover, the anti-tumor effect of quercetin is correlated with WNT/β-catenin pathway and miRNA dysregulation. In the present study, we aimed to further investigate whether quercetin c...

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Main Authors: Chunping Zhang, Yuli Hao, Yuanyuan Sun, Ping Liu
Format: Article
Language:English
Published: Elsevier 2019-06-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319310436
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spelling doaj-063d6638642b49e587a7f2f3043b23ce2020-11-24T21:55:49ZengElsevierJournal of Pharmacological Sciences1347-86132019-06-011402128136Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axisChunping Zhang0Yuli Hao1Yuanyuan Sun2Ping Liu3Department of Stomatology, Yuhuangding Hospital, Yantai, 264000, ChinaDepartment of Stomatology, Yuhuangding Hospital, Yantai, 264000, ChinaDepartment of Periodontology, Yantai Stomatological Hospital, Yantai, 264000, ChinaDepartment of Stomatology, Affiliated Hospital of Jining Medical University, Jining, 272029, China; Corresponding author. Department of Stomatology, Affiliated Hospital of Jining Medical University, No. 89 Guhuai Road, Rencheng District, Jining, 272029, China.Quercetin has potential pharmacological values in various carcinomas including oral squamous cell carcinoma (OSCC). Moreover, the anti-tumor effect of quercetin is correlated with WNT/β-catenin pathway and miRNA dysregulation. In the present study, we aimed to further investigate whether quercetin can exert its anti-tumor function by regulating miR-22 together with miR-22 downstream pathway WNT1/β-catenin in OSCC. The results of Cell Counting Kit-8 (CCK-8) and flow cytometry analyses showed that quercetin treatment and miR-22 overexpression resulted in the reduction of cell viability and the increase of cell apoptotic rate in OSCC. WNT1 was a target of miR-22, which was confirmed by bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays. RT-qPCR assay showed that quercetin promoted miR-22 expression and suppressed WNT1 and β-catenin expression in OSCC cells, whereas this effect was abrogated by miR-22 inhibitor. Moreover, miR-22 depletion weakened quercetin-mediated viability inhibition and apoptosis increase in OSCC cells. Quercetin inhibited the growth of OSCC xenograft tumors by inducing miR-22 expression and repressing WNT1/β-catenin pathway in vivo. Taken together, quercetin hampered OSCC tumorigenesis by regulating miR-22/WNT1/β-catenin pathway in OSCC, providing a deep insight into the molecular targets of quercetin in the treatment of OSCC. Keywords: Quercetin, microRNA-22, WNT1/β-catenin pathway, Oral squamous cell carcinomahttp://www.sciencedirect.com/science/article/pii/S1347861319310436
collection DOAJ
language English
format Article
sources DOAJ
author Chunping Zhang
Yuli Hao
Yuanyuan Sun
Ping Liu
spellingShingle Chunping Zhang
Yuli Hao
Yuanyuan Sun
Ping Liu
Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis
Journal of Pharmacological Sciences
author_facet Chunping Zhang
Yuli Hao
Yuanyuan Sun
Ping Liu
author_sort Chunping Zhang
title Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis
title_short Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis
title_full Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis
title_fullStr Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis
title_full_unstemmed Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis
title_sort quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microrna-22/wnt1/β-catenin axis
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2019-06-01
description Quercetin has potential pharmacological values in various carcinomas including oral squamous cell carcinoma (OSCC). Moreover, the anti-tumor effect of quercetin is correlated with WNT/β-catenin pathway and miRNA dysregulation. In the present study, we aimed to further investigate whether quercetin can exert its anti-tumor function by regulating miR-22 together with miR-22 downstream pathway WNT1/β-catenin in OSCC. The results of Cell Counting Kit-8 (CCK-8) and flow cytometry analyses showed that quercetin treatment and miR-22 overexpression resulted in the reduction of cell viability and the increase of cell apoptotic rate in OSCC. WNT1 was a target of miR-22, which was confirmed by bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays. RT-qPCR assay showed that quercetin promoted miR-22 expression and suppressed WNT1 and β-catenin expression in OSCC cells, whereas this effect was abrogated by miR-22 inhibitor. Moreover, miR-22 depletion weakened quercetin-mediated viability inhibition and apoptosis increase in OSCC cells. Quercetin inhibited the growth of OSCC xenograft tumors by inducing miR-22 expression and repressing WNT1/β-catenin pathway in vivo. Taken together, quercetin hampered OSCC tumorigenesis by regulating miR-22/WNT1/β-catenin pathway in OSCC, providing a deep insight into the molecular targets of quercetin in the treatment of OSCC. Keywords: Quercetin, microRNA-22, WNT1/β-catenin pathway, Oral squamous cell carcinoma
url http://www.sciencedirect.com/science/article/pii/S1347861319310436
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