Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21

Bray, 2018, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J. Clin., 68, 394, 10.3322/caac.21492 Chen, 2019, Nasopharyngeal carcinoma, Lancet, 394, 64, 10.1016/S0140-6736(19)30956-0 Zhang, 2019, Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma, N. Engl. J. Med., 381, 1124, 10.1056/NEJMoa1905287 Mohammad, 2019, Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer, Nat. Med., 25, 403, 10.1038/s41591-019-0376-8 Lyko, 2018, The DNA methyltransferase family: a versatile toolkit for epigenetic regulation, Nat. Rev. Genet., 19, 81, 10.1038/nrg.2017.80 Zhu, 2004, 5-Aza-2′-deoxycytidine activates the p53/p21Waf1/Cip1 pathway to inhibit cell proliferation, J. Biol. Chem., 279, 15161, 10.1074/jbc.M311703200 Montalban-Bravo, 2018, Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and management, Am. J. Hematol., 93, 129, 10.1002/ajh.24930 Agrawal, 2018, Nucleosidic DNA demethylating epigenetic drugs—a comprehensive review from discovery to clinic, Pharmacol. Ther., 188, 45, 10.1016/j.pharmthera.2018.02.006 Jiang, 2014, 5-Azacytidine enhances the radiosensitivity of CNE2 and SUNE1 cells in vitro and in vivo possibly by altering DNA methylation, PLoS ONE, 9, e93273, 10.1371/journal.pone.0093273 Wang, 2014, Involvement of microRNA-24 and DNA methylation in resistance of nasopharyngeal carcinoma to ionizing radiation, Mol. Cancer Ther., 13, 3163, 10.1158/1535-7163.MCT-14-0317 Linhart, 2007, Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing, Genes Dev., 21, 3110, 10.1101/gad.1594007 Yang, 2014, DNMT3B overexpression by deregulation of FOXO3a-mediated transcription repression and MDM2 overexpression in lung cancer, J Thorac Oncol, 9, 1305, 10.1097/JTO.0000000000000240 Chen, 2016, Involvement of DNMT 3B promotes epithelial-mesenchymal transition and gene expression profile of invasive head and neck squamous cell carcinomas cell lines, BMC Cancer, 16, 431, 10.1186/s12885-016-2468-x Roll, 2008, DNMT3b overexpression contributes to a hypermethylator phenotype in human breast cancer cell lines, Mol. Cancer, 7, 15, 10.1186/1476-4598-7-15 Nosho, 2009, DNMT3B expression might contribute to CpG island methylator phenotype in colorectal cancer, Clin Cancer Res, 15, 3663, 10.1158/1078-0432.CCR-08-2383 Girault, 2003, Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas, Clin Cancer Res, 9, 4415 Amara, 2010, DNA methyltransferase DNMT3b protein overexpression as a prognostic factor in patients with diffuse large B-cell lymphomas, Cancer Sci., 101, 1722, 10.1111/j.1349-7006.2010.01569.x Hayette, 2012, High DNA methyltransferase DNMT3B levels: a poor prognostic marker in acute myeloid leukemia, PLoS ONE, 7, e51527, 10.1371/journal.pone.0051527 Chen, 2012, The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma, Cancer, 118, 4074, 10.1002/cncr.26736 Xue, 2015, A feedback regulation between miR-145 and DNA methyltransferase 3b in prostate cancer cell and their responses to irradiation, Cancer Lett., 361, 121, 10.1016/j.canlet.2015.02.046 Bieging, 2014, Unravelling mechanisms of p53-mediated tumour suppression, Nat. Rev. Cancer, 14, 359, 10.1038/nrc3711 Gudkov, 2003, The role of p53 in determining sensitivity to radiotherapy, Nat. Rev. Cancer, 3, 117, 10.1038/nrc992 Bykov, 2018, Targeting mutant p53 for efficient cancer therapy, Nat. Rev. Cancer, 18, 89, 10.1038/nrc.2017.109 Liu, 2002, Novel gene therapy approach for nasopharyngeal carcinoma, Semin. Cancer Biol., 12, 505, 10.1016/S1044579X02000937 El-Deiry, 2016, p21(WAF1) mediates cell-cycle inhibition, relevant to cancer suppression and therapy, Cancer Res., 76, 5189, 10.1158/0008-5472.CAN-16-2055 Abbas, 2009, p21 in cancer: intricate networks and multiple activities, Nat. Rev. Cancer, 9, 400, 10.1038/nrc2657 Nie, 2019, SALL4 induces radioresistance in nasopharyngeal carcinoma via the ATM/Chk2/p53 pathway, Cancer Med., 8, 1779, 10.1002/cam4.2056 Seo, 2008, Epstein-Barr virus latent membrane protein 1 suppresses the growth-inhibitory effect of retinoic acid by inhibiting retinoic acid receptor-β2 expression via DNA methylation, Cancer Lett., 270, 66, 10.1016/j.canlet.2008.04.043 Peng, 2016, Higher methylation intensity induced by EBV LMP1 via NF-κB/DNMT3b signaling contributes to silencing of PTEN gene, Oncotarget, 7, 40025, 10.18632/oncotarget.9474 Pawlik, 2004, Role of cell cycle in mediating sensitivity to radiotherapy, Int. J. Radiat. Oncol. Biol. Phys., 59, 928, 10.1016/j.ijrobp.2004.03.005 Liu, 2015, IL-6 enriched lung cancer stem-like cell population by inhibition of cell cycle regulators via DNMT1 upregulation, Int. J. Cancer, 136, 547, 10.1002/ijc.29033 Liu, 2018, Downregulation of DNMT3A by miR-708-5p inhibits lung cancer stem cell-like phenotypes through repressing Wnt/β-catenin signaling, Clin Cancer Res, 24, 1748, 10.1158/1078-0432.CCR-17-1169 Yang, 2014, Cancer stem-like cell characteristics induced by EB virus-encoded LMP1 contribute to radioresistance in nasopharyngeal carcinoma by suppressing the p53-mediated apoptosis pathway, Cancer Lett., 344, 260, 10.1016/j.canlet.2013.11.006 Pan, 2009, Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma, J. Clin. Oncol., 27, 799, 10.1200/JCO.2008.18.9670 Mello, 2018, Deciphering p53 signaling in tumor suppression, Curr. Opin. Cell Biol., 51, 65, 10.1016/j.ceb.2017.11.005 Yu, 2019, Radiation-promoted CDC6 protein stability contributes to radioresistance by regulating senescence and epithelial to mesenchymal transition, Oncogene, 38, 549, 10.1038/s41388-018-0460-4 Zhou, 2016, Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation, Oncotarget, 7, 20691, 10.18632/oncotarget.7842 Cao, 2016, miR-125b targets DNMT3b and mediates p53 DNA methylation involving in the vascular smooth muscle cells proliferation induced by homocysteine, Exp. Cell Res., 347, 95, 10.1016/j.yexcr.2016.07.007 Zheng, 2006, p21Waf1/Cip1 plays a critical role in modulating senescence through changes of DNA methylation, J. Cell. Biochem., 98, 1230, 10.1002/jcb.20838 Powell, 2014, Contribution of p53 to metastasis, Cancer Discov., 4, 405, 10.1158/2159-8290.CD-13-0136 Chang, 2011, p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs, Nat. Cell Biol., 13, 317, 10.1038/ncb2173 Luo, 2019, FOXO3a knockdown promotes radioresistance in nasopharyngeal carcinoma by inducing epithelial-mesenchymal transition and the Wnt/β-catenin signaling pathway, Cancer Lett., 455, 26, 10.1016/j.canlet.2019.04.019 Chan, 2008, Authentication of nasopharyngeal carcinoma tumor lines, Int. J. Cancer, 122, 2169, 10.1002/ijc.23374