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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Research Article

Evaluation of Alterations in DNA Methylation of CYP3A4 Gene Upstream Regulatory Elements in Gastric Cancer and in Response to Diazinon Treatment

Author(s): Ramin Golestanian*, Ali Barzegar, Ghodrat Rahimi Mianji, Mohammad Ali Ebrahimzadeh and Behnaz Fatemi

Volume 23, Issue 3, 2022

Published on: 17 May, 2022

Page: [242 - 250] Pages: 9

DOI: 10.2174/1389200223666220324094645

Price: $65

Abstract

Background: Little is known about cytochrome P450 3A4 (CYP3A4) DNA methylation and transcription alterations in gastric cancer.

Objective: In this paper, we initially aimed to address the effect of diazinon pesticide on DNA methylation and transcription changes of the CYP3A4 gene in a human gastric cell line. In the next step, we studied the methylation differences of CpG sites within the upstream regulatory regions of the CYP3A4 gene among human gastric cancerous and healthy tissues.

Methods: For the in vitro assay, the methylation changes of the C/EBP response element and transcript level of the CYP3A4 gene were studied following treatment of the AGS cell line with various concentrations of diazinon pesticide. In the next phase, the methylation percentages of 24 CpG sites within or around the upstream regulatory elements, including near promoter, C/EBP binding site, XREM, and CLEM4, in 11 specimens of human gastric cancer tissue were compared to their adjacent healthy tissues.

Results: Treatment with 10 μM Diazinon significantly increased the CYP3A4 gene transcription by approximately 27-fold, which was correlated with the hypermethylation of 3 CpGs in C/EBP binding sites, including -5998, -5731 and -5725 (p<0.001 for all comparisons). Results of bisulfite sequencing revealed that the CpG sites which are located in -1521 (p=0.003), -1569 (p=0.027), -10813 (p=0.003), -10851 (p=0.001) and -10895 (p=0.0) bp from transcription start site, were significantly hypermethylated in cancerous tissues comparing to their healthy cohort.

Conclusion: Hypermethylation of CLEM4 and a region near the core promoter may have a significant association with gastric cancer incidence.

Keywords: CYP3A4, diazinon, gastric cancer, DNA methylation, epigenetics, malignancy.

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[1]
Abadi, A.J.; Zarrabi, A.; Hashemi, F.; Zabolian, A.; Najafi, M.; Entezari, M.; Hushmandi, K.; Aref, A.R.; Khan, H.; Makvandi, P.; Ash-rafizaveh, S.; Farkhondeh, T.; Ashrafizadeh, M.; Samarghandian, S.; Hamblin, M.R. The role of SOX family transcription factors in gastric cancer. Int. J. Biol. Macromol., 2021, 180, 608-624.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.202] [PMID: 33662423]
[2]
Feng, H.; Zhang, J.; Shi, Y.; Wang, L.; Zhang, C.; Wu, L. Long noncoding RNA LINC-PINT is inhibited in gastric cancer and predicts poor survival. J. Cell. Biochem., 2019, 120(6), 9594-9600.
[http://dx.doi.org/10.1002/jcb.28236] [PMID: 30569513]
[3]
Yazdanpanah, M.; Rahimi Feyzabad, F.; Abbaszade, K. Factors affecting avoiding the use of pesticides to greenhouse vegetables in Bandar Abbas district (Iran). Int. J. Agric. Manag. Dev., 2019, 9(3), 237-247.
[4]
Dehghani, M.H.; Kamalian, S.; Shayeghi, M.; Yousefi, M.; Heidarinejad, Z.; Agarwal, S.; Gupta, V.K. High-performance removal of diazinon pesticide from water using multi-walled carbon nanotubes. Microchem. J., 2019, 145, 486-491.
[http://dx.doi.org/10.1016/j.microc.2018.10.053]
[5]
Muhammetoglu, A.; Keyikoglu, R.; Cil, A.; Muhammetoglu, H. Integrated management of pesticides in an intensive agricultural area: A case study in Altinova, Turkey. Environ. Monit. Assess., 2019, 191(9), 599.
[http://dx.doi.org/10.1007/s10661-019-7748-x] [PMID: 31463725]
[6]
Hazarika, J.; Ganguly, M.; Mahanta, R. A computational insight into the molecular interactions of chlorpyrifos and its degradation products with the human progesterone receptor leading to endocrine disruption. J. Appl. Toxicol., 2020, 40(3), 434-443.
[http://dx.doi.org/10.1002/jat.3916] [PMID: 31889325]
[7]
Vihinen, M. Systematics for types and effects of DNA variations. BMC Genomics, 2018, 19(1), 974.
[http://dx.doi.org/10.1186/s12864-018-5262-0] [PMID: 30591019]
[8]
Zhang, B.; Zhang, X.; Jin, M.; Hu, L.; Zang, M.; Qiu, W.; Wang, S.; Liu, B.; Liu, S.; Guo, D. CagA increases DNA methylation and decreases PTEN expression in human gastric cancer. Mol. Med. Rep., 2019, 19(1), 309-319.
[PMID: 30431097]
[9]
Qian, Y.; Ji, C.; Yue, S.; Zhao, M. Exposure of low-dose fipronil enantioselectively induced anxiety-like behavior associated with DNA methylation changes in embryonic and larval zebrafish. Environ. Pollut., 2019, 249, 362-371.
[http://dx.doi.org/10.1016/j.envpol.2019.03.038] [PMID: 30909129]
[10]
Hageman, G.; Pal, T.; Nihom, J. MackenzieRoss, S.J.; van den Berg, M. Three patients with probable aerotoxic syndrome. Clin. Toxicol. (Phila.), 2020, 58(2), 139-142.
[http://dx.doi.org/10.1080/15563650.2019.1616092]
[11]
Fritz, A.; Busch, D.; Lapczuk, J.; Ostrowski, M.; Drozdzik, M.; Oswald, S. Expression of clinically relevant drug-metabolizing enzymes along the human intestine and their correlation to drug transporters and nuclear receptors: An intra-subject analysis. Basic Clin. Pharmacol. Toxicol., 2019, 124(3), 245-255.
[http://dx.doi.org/10.1111/bcpt.13137] [PMID: 30253071]
[12]
Kacevska, M.; Ivanov, M.; Wyss, A.; Kasela, S.; Milani, L.; Rane, A.; Ingelman-Sundberg, M. DNA methylation dynamics in the hepatic CYP3A4 gene promoter. Biochimie, 2012, 94(11), 2338-2344.
[http://dx.doi.org/10.1016/j.biochi.2012.07.013] [PMID: 22906825]
[13]
Ashida, R.; Okamura, Y.; Ohshima, K.; Kakuda, Y.; Uesaka, K.; Sugiura, T.; Ito, T.; Yamamoto, Y.; Sugino, T.; Urakami, K.; Kusuhara, M.; Yamaguchi, K. CYP3A4 gene is a novel biomarker for predicting a poor prognosis in hepatocellular carcinoma. Cancer Genomics Proteomics, 2017, 14(6), 445-453.
[PMID: 29109094]
[14]
Li, Y.; Tollefsbol, T.O. DNA methylation detection: Bisulfite genomic sequencing analysis. Methods Mol. Biol., 2011, 791, 11-21.
[PMID: 21913068]
[15]
Kamalipour, S.; Barzegar, A.; Shokrzadeh, M.; Nikbakhsh, N. Increased expression of CYP2E1 gene in gastric cancer may be a molecular marker for Mazandaran province population. J. Genet. Resources., 2017, 3(2), 130-136.
[16]
Khalili Tanha, G.; Barzegar, A.; Shokrzadeh, M.; Nikbakhsh, N.; Ansari, Z. Correlation between serum concentration of diazinon pesticide and breast cancer incidence in Mazandaran Province, northern Iran. Caspian J. Environ. Sci., 2020, 18(3), 197-204.
[17]
Kim, H.J.; Kim, N.; Kim, H.W.; Park, J.H.; Shin, C.M.; Lee, D.H. Promising aberrant DNA methylation marker to predict gastric cancer de-velopment in individuals with family history and long-term effects of H. pylori eradication on DNA methylation. Gastric Cancer, 2021, 24(2), 302-313.
[http://dx.doi.org/10.1007/s10120-020-01117-w] [PMID: 32915372]
[18]
Sadeghi-Amiri, L.; Barzegar, A.; Nikbakhsh-Zati, N.; Mehraban, P. Hypomethylation of the XRE -1383 site is associated with the upregula-tion of CYP1A1 in gastric adenocarcinoma. Gene, 2021, 769145216
[http://dx.doi.org/10.1016/j.gene.2020.145216] [PMID: 33069801]
[19]
Wang, X.; Wei, L.; Yang, J.; Wang, Y.; Chen, S.; Yang, K.; Meng, X.; Zhang, L. DNA methylation determines the regulation of pregnane X receptor on CYP3A4 expression. Clin. Exp. Pharmacol. Physiol., 2021, 48(2), 250-259.
[http://dx.doi.org/10.1111/1440-1681.13420] [PMID: 33048369]
[20]
Collins, J.M.; Wang, D. Cis-acting regulatory elements regulating CYP3A4 transcription in human liver. Pharmacogenet. Genomics, 2020, 30(5), 107-116.
[http://dx.doi.org/10.1097/FPC.0000000000000402] [PMID: 32301865]
[21]
Taneja, G.; Maity, S.; Jiang, W.; Moorthy, B.; Coarfa, C.; Ghose, R. Transcriptomic profiling identifies novel mechanisms of transcriptional regulation of the cytochrome P450 (Cyp)3a11 gene. Sci. Rep., 2019, 9(1), 6663.
[http://dx.doi.org/10.1038/s41598-019-43248-w] [PMID: 31040347]
[22]
Sachar, M.; Kelly, E.J.; Unadkat, J.D. Mechanisms of CYP3A induction during pregnancy: Studies in HepaRG cells. AAPS J., 2019, 21(3), 45.
[http://dx.doi.org/10.1208/s12248-019-0316-z] [PMID: 30919109]
[23]
Sun, C.; Duan, P.; Luan, C. CEBP epigenetic dysregulation as a drug target for the treatment of hematologic and gynecologic malignancies. Curr. Drug Targets, 2017, 18(10), 1142-1151.
[http://dx.doi.org/10.2174/1389450117666161228160455] [PMID: 28031014]
[24]
Zhao, S.; Wesseling, S.; Spenkelink, B.; Rietjens, I.M.C.M. Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon. Arch. Toxicol., 2021, 95(5), 1573-1593.
[http://dx.doi.org/10.1007/s00204-021-03015-1] [PMID: 33715020]
[25]
Velki, M.; Lackmann, C.; Barranco, A.; Artabe, A.E.; Rainieri, S.; Hollert, H. Pesticides diazinon and diuron increase glutathione levels and affect multixenobiotic resistance activity and biomarker responses in zebrafish (Danio rerio) embryos and larvae. Environ. Sci. Eur., 2019, 31(1), 1-18.
[http://dx.doi.org/10.1186/s12302-019-0186-0]
[26]
Ye, W.; Chen, R.; Chen, X.; Huang, B.; Lin, R.; Xie, X.; Chen, J.; Jiang, J.; Deng, Y.; Wen, J. AhR regulates the expression of human cyto-chrome P450 1A1 (CYP1A1) by recruiting Sp1. FEBS J., 2019, 286(21), 4215-4231.
[http://dx.doi.org/10.1111/febs.14956] [PMID: 31199573]
[27]
Long, H-Y.; Feng, L.; Kang, J.; Luo, Z-H.; Xiao, W-B.; Long, L-L.; Yan, X.X.; Zhou, L.; Xiao, B. Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy. Sci. Rep., 2017, 7(1), 43810.
[http://dx.doi.org/10.1038/srep43810] [PMID: 28276448]
[28]
Apprey, V.; Wang, S.; Tang, W.; Kittles, R.A.; Southerland, W.M.; Ittmann, M.; Kwabi-Addo, B. Association of genetic ancestry with DNA methylation changes in prostate cancer disparity. Anticancer Res., 2019, 39(11), 5861-5866.
[http://dx.doi.org/10.21873/anticanres.13790] [PMID: 31704810]

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