Methylomics of nitroxidative stress on precancerous cells reveals DNA methylation alteration at the transition from in situ to invasive cervical cancer

Po Hsuan Su, Yao Wen Hsu, Rui Lan Huang, Yu Chun Weng, Hui Chen Wang, Yu Chih Chen, Yueh Ju Tsai, Chiou Chung Yuan, Hung Cheng Lai

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Epigenetic dysregulation is important in cervical cancer development, but the underlying mechanism is largely unknown. Increasing evidence indicates that DNA methylation is sensitive to changes in microenvironmental factors, such as nitric oxide (NO) in the chronic inflammatory cervix. However, the epigenomic effects of NO in cancer have not been investigated. In this study, we explored the methylomic effects of nitroxidative stress in HPV-immortalized precancerous cells. Chronic NO exposure promoted the acquisition of malignant phenotypes such as cell growth, migration, invasion, and anchorage-independent growth. Epigenetic analysis confirmed hypermethylation of PTPRR. Whole-genome methylation analysis showed BOLA2B, FGF8, HSPA6, LYPD2, and SHE were hypermethylated in cells. The hypermethylation BOLA2B, FGF8, HSPA6, and SHE was confirmed in cervical scrapings from invasive cancer, but not in CIN3/CIS, CIN2 and CIN1 (p=0.019, 0.023, 0.023 and 0.027 respectively), suggesting the role in the transition from in situ to invasive process. Our results reveal that nitroxidative stress causes epigenetic changes in HPV-infected cells. Investigation of these methylation changes in persistent HPV infection may help identify new biomarkers of DNA methylation for cervical cancer screening, especially for precancerous lesions.

Original languageEnglish
Pages (from-to)65281-65291
Number of pages11
JournalOncotarget
Volume8
Issue number39
DOIs
Publication statusPublished - 2017

    Fingerprint

Keywords

  • Chronic inflammation
  • Gene specific hypermethylation
  • Nitric oxide
  • Nitroxidative stress

ASJC Scopus subject areas

  • Oncology

Cite this