Overexpression of Ribosomal RNA in the Development of Human Cervical Cancer Is Associated with rDNA Promoter Hypomethylation.
The ribosomal RNA (rRNA) gene encodes rRNA for protein synthesis. Aberrant expression of the rRNA gene has been generally observed in tumor cells and levels of its promoter methylation as an epigenetic regulator affect rRNA gene transcription. The possible relationship between expression and promoter methylation of rDNA has not been examined in human clinical cervical cancer. Here we investigate rRNA gene expression by quantitative real time PCR, and promoter methylation levels by HpaII/MspI digestion and sodium bisulfite sequencing in the development of human cervical cancer. We find that indeed rRNA levels are elevated in most of cervical intraepithelial neoplasia (CIN) specimens as compared with non-cancer tissues. The rDNA promoter region in cervical intraepithelial neoplasia (CIN) tissues reveals significant hypomethylation at cytosines in the context of CpG dinucleotides, accompanied with rDNA chromatin decondensation. Furthermore treatment of HeLa cells with the methylation inhibitor drug 5-aza-2'-deoxycytidine (DAC) demonstrates the negative correlation between the expression of 45S rDNA and the methylation level in the rDNA promoter region. These data suggest that a decrease in rDNA promoter methylation levels can result in an increase of rRNA synthesis in the development of human cervical cancer.
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.
Hong
H
Zhou
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.
Yapei
Y
Wang
Department of Gynecology and Obstetrics, Zhongnan Hospital, Wuhan University, Wuhan, China.
Qiongying
Q
Lv
Department of Gynecology and Obstetrics, Zhongnan Hospital, Wuhan University, Wuhan, China.
Juan
J
Zhang
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.
Qing
Q
Wang
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.
Fei
F
Gao
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.
Haoli
H
Hou
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.
Hao
H
Zhang
Department of Gynecology and Obstetrics, Zhongnan Hospital, Wuhan University, Wuhan, China.
Wei
W
Zhang
State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, China.
Lijia
L
Li
D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004275:DNA, Ribosomal / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia
D002843:Chromatin; D004275:DNA, Ribosomal; D012335:RNA, Ribosomal
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