Gene regulation mediated by microRNAs in response to green tea polyphenol EGCG in mouse lung cancer

BMC Genomics

Research

Hong Zhou¹  Mary Qu Yang²  Youping Deng³  Jayson X Chen⁴  Chung S Yang⁴  Hong Wang⁴ 

[1] Department of Mathematics, University of Saint Joseph, 1678 Asylum Avenue, 06117, West Hartford, CT, USA;MidSouth Bioinformatics Center, Department of Information Science, George W. Donaghey College of Engineering and Information Technology, University of Arkansas at Little Rock, 2801 S. University Avenue, 72204, Little Rock, Arkansas, USA;Joint Bioinformatics Graduate Program, University of Arkansas at Little Rock and University of Arkansas for Medical Sciences, 72204, Little Rock, Arkansas, USA;Rush University Cancer Center, and Departments of Internal Medicine and Biochemistry, Rush University Medical Center, 60612, Chicago, Illinois, USA;Susan L. Cullman Laboratory for Cancer Research, Department of Chemical Biology and Centre for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, 08854, Piscataway, NJ, USA;

关键词: EGCG;    Lung Cancer Cell Line;    miRNA Profile;    mRNA Expression Profile;    EGCG Treatment;   

DOI  :  10.1186/1471-2164-15-S11-S3

来源: Springer

【 摘 要 】

BackgroundEpigallocatechin-3-gallate (EGCG) has been demonstrated to inhibit cancer in experimental studies through its antioxidant activity and modulations on cellular functions by binding specific proteins. We demonstrated previously that EGCG upregulates the expression of microRNA (i.e. miR-210) by binding HIF-1α, resulting in reduced cell proliferation and anchorage-independent growth. However, the binding affinities of EGCG to HIF-1α and many other targets are higher than the EGCG plasma peak level in experimental animals administered with high dose of EGCG, raising a concern whether the microRNA regulation by HIF-1α is involved in the anti-cancer activity of EGCG in vivo.ResultsWe employed functional genomic approaches to elucidate the role of microRNA in the EGCG inhibition of tobacco carcinogen-induced lung tumors in A/J mice. By analysing the microRNA profiles, we found modest changes in the expression levels of 21 microRNAs. By correlating these 21 microRNAs with the mRNA expression profiles using the computation methods, we identified 26 potential targeted genes of the 21 microRNAs. Further exploration using pathway analysis revealed that the most impacted pathways of EGCG treatment are the regulatory networks associated to AKT, NF-κB, MAP kinases, and cell cycle, and the identified miRNA targets are involved in the networks of AKT, MAP kinases and cell cycle regulationConclusionsThese results demonstrate that the miRNA-mediated regulation is actively involved in the major aspects of the anti-cancer activity of EGCG in vivo.

【 授权许可】

Unknown   
© Zhou et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.