Identification of aberrant DNA methylation involved in chemoradiation-resistant HCT116 cells via methylation-specific microarray

Wei Xiong; Yun-Feng Li; Shan Liu; Ting Chen; Hong-Tao Zhang; Zhi-Bin Yang; Ying-Ying Ding; De-Pei Gao; Guan-Shun Wang; Jian Dong

doi:10.1007/s13273-016-0039-5

Molecular & Cellular Toxicology

December 2016, Volume 12, Issue 4, pp 345–357

Identification of aberrant DNA methylation involved in chemoradiation-resistant HCT116 cells via methylation-specific microarray

Authors
Authors and affiliations

Wei Xiong
Yun-Feng Li
Shan Liu
Ting Chen
Hong-Tao Zhang
Zhi-Bin Yang
Ying-Ying Ding
De-Pei Gao
Guan-Shun Wang
Jian DongEmail author

Original Paper

First Online:: 07 January 2017

Received:: 25 January 2016
Accepted:: 20 July 2016

DOI: 10.1007/s13273-016-0039-5

Cite this article as:: Xiong, W., Li, YF., Liu, S. et al. Mol. Cell. Toxicol. (2016) 12: 345. doi:10.1007/s13273-016-0039-5

31 Downloads

Abstract

Preoperative 5-fluorouracil (5-FU) based chemoradiation is regarded as the standard treatment for locally advanced colorectal cancer (CRC). However, advances in using 5-FU in chemoradiotherapy treatment of CRC are limited by the resistant to the chemoradiotherapy. It has been demonstrated that aberrant methylation contributes to radioresistance in a human colorectal tumor cell line. So we analyzed the differential DNA methylation patterns by methylationspecific microarray in a 5-FU-based concurrent chemoradiotherapy resistance cell model which was established by using human CRC cell line HCT116. As a result, we detected a total of 3719 hypomethylated sites and 27940 hypermethylated sites in CRR cells compared to the control. Furthermore, we analyzed top 10 GO terms involved in significantly differential DNA methylation patterns resulted from the 5-FU-based CRR through GO analyses. To further explore the molecular basis of 5-FU-based CRR in CRC cells, CYP1B1 and CYP2C9 genes expression level were shown down regulated by qRT-PCR. These findings might provide a novel insight for chemoradiation resistance in CRC and provide a potential therapy method in CRC patients.

Keywords

DNA methylation Chemoradiation-resistant Colorectal cancer HCT116 cells

Supplementary material

13273_2016_39_MOESM1_ESM.pdf (286 kb)

Identification of aberrant DNA methylation involved in chemoradiation-resistant HCT116 cells via methylation-specific microarray

References

1.
Chen, Y.-S., Xu, S.-X., Ding, Y.-B., Huang, X.-E. & Deng, B. Helicobacter pylori Infection and the risk of colorectal adenoma and adenocarcinoma: an updated meta-analysis of different testing methods. APJCP 14: 7613–7619 (2012).Google Scholar
2.
Chen, Y.-S. et al. Colorectal cancer screening in highrisk populations: a survey of cognition among medical professionals in Jiangsu, China. APJCP 14:6487–6491 (2013).Google Scholar
3.
Goyle, S. & Maraveyas, A. Chemotherapy for colorectal cancer. Digest Surg 22:401–414 (2005).CrossRefGoogle Scholar
4.
Mamon, H. J. & Tepper, J. E. Combination chemoradiation therapy: the whole is more than the sum of the parts. J Clin Oncol 32:367–369 (2014).CrossRefPubMedGoogle Scholar
5.
Wan, J., Gai, Y., Li, G., Tao, Z. & Zhang, Z. Incidence of chemotherapy-and chemoradiotherapy-induced amenorrhea in premenopausal women with stage II/III colorectal cancer. Clin Colorectal Cancer 14:31–34 (2015).CrossRefPubMedGoogle Scholar
6.
Appelt, A. L. et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol 16:919–927 (2015).CrossRefPubMedGoogle Scholar
7.
Lee, J. H. et al. The influence of the treatment response on the impact of resection margin status after preoperative chemoradiotherapy in locally advanced rectal cancer. BMC Cancer 13:576 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
8.
Sobrero, A. F., Aschele, C. & Bertino, J. R. Fluorouracil in colorectal cancer—a tale of two drugs: implications for biochemical modulation. J Clin Oncol 15:368–381 (1997).PubMedGoogle Scholar
9.
Gong, J.-P. et al. Outcomes based on risk assessment of anastomotic leakage after rectal cancer surgery. APJCP 15:707–712 (2013).Google Scholar
10.
Kye, B.-H. & Cho, H.-M. Overview of Radiation Therapy for Treating Rectal Cancer. Ann Coloproctol 30: 165–174 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
11.
Gantt, G. A. et al. Gene expression profile is associated with chemoradiation resistance in rectal cancer. Colorectal Dis 16:57–66 (2014).CrossRefPubMedGoogle Scholar
12.
Kim, Y., Joo, K. M., Jin, J. & Nam, D. H. Cancer stem cells and their mechanism of chemo-radiation resistance. Int J Stem Cells 2:109–114 (2009).CrossRefPubMedPubMedCentralGoogle Scholar
13.
Chan, M. F., Liang, G. & Jones, P. A. Relationship between transcription and DNA methylation. Curr Top Microbiol 249:75–86 (2000).Google Scholar
14.
Guz, J., Foksinski, M. & Olinski, R. Mechanism of DNA methylation and demethylation—its role in control of genes expression. Postepy Biochem 56:7–15 (2010).PubMedGoogle Scholar
15.
Hendrich, B. & Bird, A. Mammalian methyltransferases and methyl-CpG-binding domains: proteins involved in DNA methylation. Curr Top Microbiol 249: 55–74 (2000).Google Scholar
16.
Hsieh, C. L. Dynamics of DNA methylation pattern. Curr Opin Genet Dev 10:224–228 (2000).CrossRefPubMedGoogle Scholar
17.
Song, C. X. & He, C. Balance of DNA methylation and demethylation in cancer development. Genome Biol 13:173 (2012).CrossRefPubMedPubMedCentralGoogle Scholar
18.
Kulis, M. & Esteller, M. DNA methylation and cancer. Advances in Genetics 70:27–56 (2010).PubMedGoogle Scholar
19.
Bibikova, M. et al. High density DNA methylation array with single CpG site resolution. Genomics 98:288–295 (2011).CrossRefPubMedGoogle Scholar
20.
Kim, W.-J., Vo, Q. N., Shrivastav, M., Lataxes, T. A. & Brown, K. D. Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene 21:3864–3871 (2002).CrossRefPubMedGoogle Scholar
21.
Kim, E. H., Park, A. K., Dong, S. M., Ahn, J. H. & Park, W. Y. Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines. Oncogene 29:4725–4731 (2010).CrossRefPubMedGoogle Scholar
22.
Bae, J. H. et al. Identification of radiation-induced aberrant hypomethylation in colon cancer. BMC Genomics 16:56 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
23.
Dou, X. et al. Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases. APJCP 14:3881–3885 (2013).PubMedGoogle Scholar
24.
Chen, Y., Jungsuwadee, P., Vore, M., Butterfield, D. A. & St Clair, D. K. Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol Interv 7:147 (2007).CrossRefPubMedGoogle Scholar
25.
Ma, X. et al. Nrf2 knockdown by shRNA inhibits tumor growth and increases efficacy of chemotherapy in cervical cancer. Cancer Chemoth Phar 69:485–494 (2012).CrossRefGoogle Scholar
26.
Wang, X.-J. et al. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis 29:1235–1243 (2008).CrossRefPubMedPubMedCentralGoogle Scholar
27.
Nelson, D. R. et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenet Genom 6:1–42 (1996).CrossRefGoogle Scholar
28.
Park, B. K., Pirmohamed, M. & Kitteringham, N. R. The role of cytochrome P450 enzymes in hepatic and extrahepatic human drug toxicity. Pharmacol Therapeut 68:385–424 (1995).CrossRefGoogle Scholar
29.
Oliw, E. H. Oxygenation of polyunsaturated fatty acids by cytochrome P450 monooxygenates. Prog Lipid Res 33:329–354 (1994).CrossRefPubMedGoogle Scholar
30.
Nebert, D. W. & Dalton, T. P. The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer 6:947–960 (2006).CrossRefPubMedGoogle Scholar
31.
Shimada, T. & Fujii-Kuriyama, Y. Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and1B1. Cancer Sci 95:1–6 (2004).CrossRefPubMedGoogle Scholar
32.
Chambers, D., Wilson, L., Maden, M. & Lumsden, A. RALDH-independent generation of retinoic acid during vertebrate embryogenesis by CYP1B1. Development 134:1369–1383 (2007).
33.
Choudhary, D., Jansson, I., Stoilov, I., Sarfarazi, M. & Schenkman, J. B. Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos 32:840–847 (2004).CrossRefPubMedGoogle Scholar
34.
Murray, G. I., Melvin, W. T., Greenlee, W. F. & Burke, M. D. Regulation, function, and tissue-specific expression of cytochrome P450 CYP1B1. Ann Rev Pharmacol 41:297–316 (2001).CrossRefGoogle Scholar
35.
Nakajima, T. et al. CAR CINOGENE SIS: Expression of cytochrome P450s and glutathione S-transferases in human esophagus with squamous-cell carcinomas. Carcinogenesis 17:1477–1481 (1996).CrossRefPubMedGoogle Scholar
36.
Ronghe, A. M., Chatterjee, A., Padhye, S. & Bhat, H. K. Differential regulation of estrogen metabolizing CYP1A1 and CYP1B1 enzymes by novel resveratrol analogs in breast cancer cells. Cancer Res 75:Abstract nr 4648 (2015).CrossRefGoogle Scholar
37.
Androutsopoulos, V. P. et al. Expression profile of CYP1A1 and CYP1B1 enzymes in colon and bladder tumors. PLoS One 8:e82487 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
38.
Habano, W. et al. CYP1B1, but not CYP1A1, is downregulated by promoter methylation in colorectal cancers. Int J Oncol 34:1085 (2009).CrossRefPubMedGoogle Scholar
39.
Patel, S. et al. Interleukin-6 mediated upregulation of CYP1B1 and CYP2E1 in colorectal cancer involves DNA methylation, miR27b and STAT3. Brit J Cancer 111:2287–2296 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
40.
Le Morvan, V. et al. Role of CYP1B1 gene polymorphisms in anticancer drug cytotoxicity as studied on isogenic cell lines. Cancer Res 72:Abstract nr 1871 (2012).CrossRefGoogle Scholar
41.
Cui, J. et al. Design and Synthesis of New a-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors to Overcome Docetaxel-resistance Associated with CYP1B1 Overexpression. J Med Chem 58:3534–3547 (2015).CrossRefPubMedGoogle Scholar
42.
Narjoz, C. et al. Important Role of CYP2J2 in Protein Kinase Inhibitor Degradation: A Possible Role in Intratumor Drug Disposition and Resistance. PLoS One 9:e95532 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
43.
Potter, G. et al. The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. Brit J Cancer 86:774–778 (2002).CrossRefPubMedPubMedCentralGoogle Scholar
44.
Gonzalez, F. J. Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res-fund Mol M 569:101–110 (2005).CrossRefGoogle Scholar
45.
Chen, Z.-H. et al. Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis 25: 2005–2013 (2004).CrossRefPubMedGoogle Scholar
46.
Boruban, M., Yasar, U., Babaoglu, M., Sencan, O. & Bozkurt, A. Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemotherapy 18:421–424 (2006).CrossRefGoogle Scholar
47.
Martínez, C. et al. Association of CYP2C9 genotypes leading to high enzyme activity and colorectal cancer risk. Carcinogenesis 22:1323–1326 (2001).CrossRefPubMedGoogle Scholar
48.
Schmelzle, M. et al. Esophageal cancer proliferation is mediated by cytochrome P450 2C9 (CYP2C9). Prostag Oth Lipid M 94:25–33 (2011).CrossRefGoogle Scholar
49.
Xiong, W. et al. Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells. APJCP 16:3395–3402 (2015).PubMedGoogle Scholar
50.
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc B 57:289–300 (1995).Google Scholar
51.
Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57 (2008).CrossRefGoogle Scholar

Copyright information

Authors and Affiliations

Wei Xiong
- 1
Yun-Feng Li
- 2
Shan Liu
- 3
Ting Chen
- 1
Hong-Tao Zhang
- 2
Zhi-Bin Yang
- 2
Ying-Ying Ding
- 4
De-Pei Gao
- 4
Guan-Shun Wang
- 4
Jian Dong
- 5
Email author

1.Department of Radiation Oncology, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityKunmingChina
2.Department of Colorectal Surgery, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityKunmingChina
3.Department of Integrated Chinese and Western Medicine, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityKunmingChina
4.Department of Medical Imaging, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityKunmingChina
5.Department of Medical Oncology, Yunnan Cancer HospitalThe Third Affiliated Hospital of Kunming Medical UniversityKunmingChina

Personalised recommendations

Article actions

Unlimited access to the full article
Instant download
Include local sales tax if applicable

Identification of aberrant DNA methylation involved in chemoradiation-resistant HCT116 cells via methylation-specific microarray

Abstract

Keywords

Supplementary material

Copyright information

Authors and Affiliations

Personalised recommendations

Cookies