Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Epigenetic Regulation of Human Riboflavin Transporter 2(hRFT2) in Cervical Cancers from Uighur Women

  • Ma, Jun-Qi (Department of Gynecology, the First Affiliated Hospital, Medical University of Xinjiang) ;
  • Kurban, Shajidai (Department of Pathology, College of Basic Medicine, Medical University of Xinjiang) ;
  • Zhao, Jun-Da (Department of Gynecology, the First Affiliated Hospital, Medical University of Xinjiang) ;
  • Li, Qiao-Zhi (Department of Pathology, College of Basic Medicine, Medical University of Xinjiang) ;
  • Hasimu, Ayshamgul (Department of Pathology, College of Basic Medicine, Medical University of Xinjiang)
  • Published : 2014.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

In the present study, we studied the hypermethylation of the human riboflavin transporter 2 (hRFT2) gene and regulation of protein expression in biopsies from resected tissues from Uighur cervical squamous cell carcinoma (CSCC) patients and their neighboring normal tissues. hRFT2 gene promoter region methylation sequences were mapped in cervical cancer cell line SiHa by bisulfite-sequencing PCR and quantitative detection of methylated DNA from 30 pairs of Uighur's CSCCs and adjacent normal tissues by MassARRAY (Sequenom, San Diego, CA, USA) and hRFT2 protein expression was analyzed by immunohistochemistry. In SiHa, we identified 2 CG sites methylated from all of 12CpG sites of the hRFT2 gene. Analysis of the data from quantitative analysis of single CpG site methylation by Sequenom MassARRAY platform showed that the methylation level between two CpG sites (CpG 2 and CpG 3) from CpG 1~12 showed significant differences between CSCC and neighboring normal tissues. However, the methylation level of whole target CpG fragments demonstrated no significant variation between CSCC ($0.476{\pm}0.020$) and neighboring normal tissues ($0.401{\pm}0.019$, p>0.05). There was a tendency for translocation the hRFT2 proteins from cytoplasm/membrane to nucleus in CSCC with increase in methylation of CpG 2 and CpG 3 in hRFT2gene promoter regions, which may relate to the genesis of CSCC. Our results suggested that epigenetic modifications are responsible for aberrant expression of the hRFT2 gene, and may help to understand mechanisms of cervical carcinogenesis.

Keywords

References

  1. Binh H, Yang, Freddie I, et al (2004). cervical cancer as a priority for prevention in different world regions: an evaluation using years of life lost. Int J Cancer, 109, 418-24. https://doi.org/10.1002/ijc.11719
  2. Brock KE, Berry G, Mock PA, et al (1988). Nutrients in diet and plasma and risk of in situ cervical cancer. J Natl Cancer Inst, 80, 580-5. https://doi.org/10.1093/jnci/80.8.580
  3. De Souza ACS, Kodach L, Gadelha FR, et al (2006). A promising action of riboflavin as a mediator of leukaemia cell death. Apoptosis, 11, 1761-71. https://doi.org/10.1007/s10495-006-9549-2
  4. Fujimura M, Yamamoto S, Murata T, et al (2010). Functional characteristics of the human ortholog of riboflavin transporter 2 and riboflavin-responsive expression of its rat ortholog in the small intestine indicate its involvement in riboflavin absorption. J Nutr, 140, 1722-7. https://doi.org/10.3945/jn.110.128330
  5. Hernandez BY, McDuffie K, Wilkens LR, et al (2003). Diet and premalignant lesions of the cervix: evidence of a protective role of folate, riboflavin, thiamine and vitamin B12. Cancer Causes Control, 14, 859-70. https://doi.org/10.1023/B:CACO.0000003841.54413.98
  6. IARC (1995). Monograph on Cancer, Human Papillomavirus. World Health Organization.
  7. Ingrid C, Cristina B, Eleonora M, et al (2011). Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues. BMC Cancer, 11, 244. https://doi.org/10.1186/1471-2407-11-244
  8. Julaiti Ainiwaer, Abuduaini Tuerhong, Ayshamgul Hasim, et al. (2012). Association of the plasma riboflavin levels and riboflavin transporter (C20orf54) gene statuses in Kazak esophageal squamous cell carcinoma patients. Mol Biol Rep, 40, 3769-75.
  9. Kim YI (2004). Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers, 13, 511-9.
  10. Lalai Suzuk, Yu-Hua Peng, Fu-sheng Zhou (2006). Analysis of the cervical cancer distribution in Xinjiang. J Xinjiang Medical University, 29, 569-71.
  11. Maynur Eli, De-Sheng Li, Wei-Wei Zhang, et al (2012). Decreased blood riboflavin levels are correlated with defective expression of the riboflavin transporter 2 gene in gastric cancer. World J Gastroenterol, 18, 3112-8. https://doi.org/10.3748/wjg.v18.i24.3112
  12. Murphy SJ, Anderson LA, Ferguson HR, et al (2010). Dietary antioxidant and mineral intake in humans is associated with reduced risk of esophageal adenocarcinoma but not reflux esophagitis or Barrett's esophagus. J Nutr, 140, 1757-63. https://doi.org/10.3945/jn.110.124362
  13. Pangrekar J, Krishnaswamy K, Jagadeesan V (1993). Effects of riboflavin deficiency and riboflavin administration on carcinogen-DNA binding. Food Chem Toxicol, 31, 745-50. https://doi.org/10.1016/0278-6915(93)90146-P
  14. Powers HJ (2003). Riboflavin (vitamin B-2) and health. Am J Clin Nutr, 77, 1352-60.
  15. Powers HJ (2005). Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer. J Nutr, 135, 2960-6.
  16. Sugiura T, Kato Y, Kubo Y, Tsuji A (2011). Mutation in an adaptor protein PDZK1 affects transport activity of organic cation transporter OCTNs and oligopeptide transporter PEPT2. Drug Metab Pharmacokinet, 21, 375-83.
  17. Taira K (2006). Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature, 441, 1176. https://doi.org/10.1038/nature04952
  18. Yonezawa A, Masuda S, Katsura T, et al (2008). Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. Am J Physiol Cell Physiol, 295, 632-41.
  19. Zur Hausen H (2002). Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer, 2, 342-50. https://doi.org/10.1038/nrc798

Cited by

  1. Cervical Cancer Gene Therapy by Gene Loaded PEG-PLA Nanomedicine vol.15, pp.12, 2014, https://doi.org/10.7314/APJCP.2014.15.12.4915
  2. C13orf18 and C1orf166 (MULAN) DNA Genes Methylation are Not Associated with Cervical Cancer and Precancerous Lesions of Human Papillomavirus Genotypes in Iranian Women vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6745
  3. Vitamin B2 Intake and the Risk of Colorectal Cancer: a Meta-Analysis of Observational Studies vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.909
  4. Overexpression of riboflavin transporter 2 contributes toward progression and invasion of glioma vol.27, pp.15, 2016, https://doi.org/10.1097/WNR.0000000000000674
  5. SLC52A3 expression is activated by NF-κB p65/Rel-B and serves as a prognostic biomarker in esophageal cancer vol.75, pp.14, 2018, https://doi.org/10.1007/s00018-018-2757-4