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Hypomethylated CpG around the transcription start site enables TERT expression and HPV16 E6 regulates TERT methylation in cervical cancer cells
Jiang, Jing; Zhao, Li-Jun; Zhao, Chao; Zhang, Guo; Zhao, Yun; Li, Jing-Ran; Li, Xiao-Ping; Wei, Li-Hui
关键词Cervix Neoplasms Telomerase Human Papillomavirus E6 Tert Dna Methylation
刊名GYNECOLOGIC ONCOLOGY
2012-03-01
DOI10.1016/j.ygyno.2011.11.023
124期:3页:534-541
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Obstetrics & Gynecology
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]Oncology ; Obstetrics & Gynecology
关键词[WOS]TELOMERASE-REVERSE-TRANSCRIPTASE ; PAPILLOMAVIRUS TYPE-16 E6 ; CATALYTIC SUBUNIT ; HTERT GENE ; PROMOTER ACTIVITY ; DNA METHYLATION ; INVASIVE CANCER ; C-MYC ; HYPERMETHYLATION ; DIAGNOSIS
英文摘要

Objective. The human papillomavirus (HPV) oncoprotein, E6, activates telomerase reverse transcriptase (TERT) expression and causes cellular immortalization. It remains unclear whether E6 affects TERT transcription by altering DNA methylation profiles. In this study, we explored the methylation status of the TERT promoter in cervical cancer cell lines and its variations after E6 was silenced by RNAi.

Methods. Three kinds of cervical cell lines (HPV16 positive: CaSki and SiHa; HPV18 positive: HeLa), were taken to analyze the methylation status of the TERT promoter by methylation-specific polymerase chain reaction (MSP) and bisulfite sequencing (BS). Stealth RNAi was transiently transfected to these cell lines to silence the expression of HPV16/18 E6, and the subsequent changes of TERT mRNA levels and TERT promoter DNA methylation were examined.

Results. Hypomethylation of the DNA around the TERT transcription start site (-156 to + 162 bp) was functionally related to its transcription. After transfection with Stealth RNAi, the levels of HPV16/18 E6 and TERT mRNA were greatly decreased. The methylated CpG around the transcription start sites in CaSki and SiHa cells were statistically increased (respectively P=0.016, P=0.000). However, there was no significant difference in HeLa cells (P=0.128).

Conclusion. Hypomethylated CpG around the transcription start site enables the expression of TERT in cervical cancer cells. Our results show for the first time that HPV16 E6 can promote TERT transcription through demethylating the DNA sequence around the TERT transcription start site in cervical squamous cancer cells. (C) 2011 Elsevier Inc. All rights reserved.

语种英语
所属项目编号81001157
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000300751900028
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51220
专题北京大学第二临床医学院
作者单位Peking Univ, Peoples Hosp, Dept Obstet & Gynecol, Beijing 100044, Peoples R China
推荐引用方式
GB/T 7714
Jiang, Jing,Zhao, Li-Jun,Zhao, Chao,et al. Hypomethylated CpG around the transcription start site enables TERT expression and HPV16 E6 regulates TERT methylation in cervical cancer cells[J]. GYNECOLOGIC ONCOLOGY,2012,124(3):534-541.
APA Jiang, Jing.,Zhao, Li-Jun.,Zhao, Chao.,Zhang, Guo.,Zhao, Yun.,...&Wei, Li-Hui.(2012).Hypomethylated CpG around the transcription start site enables TERT expression and HPV16 E6 regulates TERT methylation in cervical cancer cells.GYNECOLOGIC ONCOLOGY,124(3),534-541.
MLA Jiang, Jing,et al."Hypomethylated CpG around the transcription start site enables TERT expression and HPV16 E6 regulates TERT methylation in cervical cancer cells".GYNECOLOGIC ONCOLOGY 124.3(2012):534-541.
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