Reactive Oxygen Species Regulate ERBB2 and ERBB3 Expression Via MiR-199a/125b and DNA Methylation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2012 Nov 14

PMID 23146892

Citations 68

Authors

Jun He

Qing Xu

Yi Jing

Faton Agani

Xu Qian

Richard Carpenter

Qi Li

Xin-Ru Wang

Stephen S Peiper

Zhimin Lu

Ling-Zhi Liu

Bing-Hua Jiang

Affiliations

Soon will be listed here.

Abstract

Overexpression of ERBB2 or ERBB3 is associated with cancer development and poor prognosis. In this study, we show that reactive oxygen species (ROS) induce both ERBB2 and ERBB3 expression in vitro and in vivo. We also identify that miR-199a and miR-125b target ERBB2 and/or ERBB3 in ovarian cancer cells, and demonstrate that ROS inhibit miR-199a and miR-125b expression through increasing the promoter methylation of the miR-199a and miR-125b genes by DNA methyltransferase 1. These findings reveal that ERBB2 and ERBB3 expression is regulated by ROS via miR-199a and miR-125b downregulation and DNA hypermethylation.

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References

Scott G, Goga A, Bhaumik D, Berger C, Sullivan C, Benz C . Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem. 2006; 282(2):1479-86. DOI: 10.1074/jbc.M609383200. View

Cheung H, Davis A, Lee T, Pang A, Nagrani S, Rennert O . Methylation of an intronic region regulates miR-199a in testicular tumor malignancy. Oncogene. 2011; 30(31):3404-15. PMC: 3117973. DOI: 10.1038/onc.2011.60. View

Nana-Sinkam S, Croce C . MicroRNAs as therapeutic targets in cancer. Transl Res. 2011; 157(4):216-25. DOI: 10.1016/j.trsl.2011.01.013. View

Franco R, Schoneveld O, Georgakilas A, Panayiotidis M . Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett. 2008; 266(1):6-11. DOI: 10.1016/j.canlet.2008.02.026. View

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

Miranda K, Huynh T, Tay Y, Ang Y, Tam W, Thomson A . A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. 2006; 126(6):1203-17. DOI: 10.1016/j.cell.2006.07.031. View

Ono M, Kuwano M . Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clin Cancer Res. 2006; 12(24):7242-51. DOI: 10.1158/1078-0432.CCR-06-0646. View

Steffensen K, Waldstrom M, Andersen R, Olsen D, Jeppesen U, Knudsen H . Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors. Int J Oncol. 2008; 33(1):195-204. View

Iorio M, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P . MicroRNA signatures in human ovarian cancer. Cancer Res. 2007; 67(18):8699-707. DOI: 10.1158/0008-5472.CAN-07-1936. View

10.

Sasaki N, Kudoh K, Kita T, Tsuda H, Furuya K, Kikuchi Y . Effect of HER-2/neu overexpression on chemoresistance and prognosis in ovarian carcinoma. J Obstet Gynaecol Res. 2007; 33(1):17-23. DOI: 10.1111/j.1447-0756.2007.00486.x. View

11.

OHagan H, Wang W, Sen S, DeStefano Shields C, Lee S, Zhang Y . Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. Cancer Cell. 2011; 20(5):606-19. PMC: 3220885. DOI: 10.1016/j.ccr.2011.09.012. View

12.

Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M . Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006; 160(1):1-40. DOI: 10.1016/j.cbi.2005.12.009. View

13.

Tsai K, Kao H, Chen H, Chen S, Lin W . Epigenetic control of the expression of a primate-specific microRNA cluster in human cancer cells. Epigenetics. 2009; 4(8):587-92. DOI: 10.4161/epi.4.8.10230. View

14.

Servidei T, Riccardi A, Mozzetti S, Ferlini C, Riccardi R . Chemoresistant tumor cell lines display altered epidermal growth factor receptor and HER3 signaling and enhanced sensitivity to gefitinib. Int J Cancer. 2008; 123(12):2939-49. DOI: 10.1002/ijc.23902. View

15.

Zhang Y, Yan L, Wu Q, Du Z, Chen J, Liao D . miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer. Cancer Res. 2011; 71(10):3552-62. DOI: 10.1158/0008-5472.CAN-10-2435. View

16.

Dolado I, Swat A, Ajenjo N, De Vita G, Cuadrado A, Nebreda A . p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis. Cancer Cell. 2007; 11(2):191-205. DOI: 10.1016/j.ccr.2006.12.013. View

17.

OHagan H, Mohammad H, Baylin S . Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. PLoS Genet. 2008; 4(8):e1000155. PMC: 2491723. DOI: 10.1371/journal.pgen.1000155. View

18.

Godshalk S, Melnik-Martinez K, Pasquinelli A, Slack F . MicroRNAs and cancer: a meeting summary of the eponymous Keystone Conference. Epigenetics. 2010; 5(2):164-8. DOI: 10.4161/epi.5.2.11162. View

19.

Zeineldin R, Muller C, Stack M, Hudson L . Targeting the EGF receptor for ovarian cancer therapy. J Oncol. 2010; 2010:414676. PMC: 2801454. DOI: 10.1155/2010/414676. View

20.

Xia C, Meng Q, Liu L, Rojanasakul Y, Wang X, Jiang B . Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res. 2007; 67(22):10823-30. DOI: 10.1158/0008-5472.CAN-07-0783. View