Increased Oxidative Stress and RUNX3 Hypermethylation in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma (HCC) and Induction of RUNX3 Hypermethylation by Reactive Oxygen Species in HCC Cells

Poungpairoj, Poonsin; Whongsiri, Patcharawalai; Suwannasin, Surasit; Khlaiphuengsin, Apichaya; Tangkijvanich, Pisit; Boonla, Chanchai

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자료유형: 학술저널

저자정보: Poungpairoj, Poonsin (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) Whongsiri, Patcharawalai (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) Suwannasin, Surasit (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) Khlaiphuengsin, Apichaya (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) Tangkijvanich, Pisit (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University) Boonla, Chanchai (Department of Biochemistry, Faculty of Medicine, Chulalongkorn University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제13호

발행연도: 2015.1

수록면: 5,343 - 5,348 (6page)

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Promoter hypermethylation of the runt-related transcription factor 3 (RUNX3) gene is associated with increased risk of hepatocellular carcinoma (HCC). Oxidative stress plays a vital role in both carcinogenesis and progression of HCC. However, whether oxidative stress and RUNX3 hypermethylation in HCC have a cause-and-effect relationship is not known. In this study, plasma protein carbonyl and total antioxidant capacity (TAC) in patients with hepatitis B virus (HBV)-associated HCC (n=60) and age-matched healthy subjects (n=80) was determined. RUNX3 methylation in peripheral blood mononuclear cells (PBMC) of subjects was measured by methylation-specific PCR. Effect of reactive oxygen species (ROS) on induction of RUNX3 hypermethylation in HCC cells was investigated. Plasma protein carbonyl content was significantly higher, whereas plasma TAC was significantly lower, in HCC patients than healthy controls. Based on logistic regression, increased plasma protein carbonyl and decreased plasma TAC were independently associated with increased risk for HCC. PBMC RUNX3 methylation in the patient group was significantly greater than in the healthy group. RUNX3 methylation in hydrogen peroxide ($H_2O_2$)-treated HepG2 cells was significantly higher than in untreated control cells. In conclusion, increase in oxidative stress in Thai patients with HBV-associated HCC was demonstrated. This oxidative increment was independently associated with an increased risk for HCC development. RUNX3 in PBMC was found to be hypermethylated in the HCC patients. In vitro, RUNX3 hypermethylation was experimentally induced by $H_2O_2$. Our findings suggest that oxidative stress is a cause of RUNX3 promoter hypermethylation in HCC cells.

#HCC #HBV #oxidative stress #ROS #RUNX3 hypermethylation #DNA methylation

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