A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer

Jialou Zhu; Zhimao Jiang; Fei Gao; Xueda Hu; Liang Zhou; Jiahao Chen; Huijuan Luo; Jihua Sun; Song Wu; Yonghua Han; Guangliang Yin; Maoshan Chen; Zujing Han; Xianxin Li; Yi Huang; Weixing Zhang; Fangjian Zhou; Tong Chen; Pingping Fa; Yong Wang; Liang Sun; Huimin Leng; Fenghao Sun; Yuchen Liu; Mingzhi Ye; Huanming Yang; Zhiming Cai; Yaoting Gui; Xiuqing Zhang

doi:10.1371/journal.pone.0028223

A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer

Jialou Zhu, Zhimao Jiang, Fei Gao, Xueda Hu, Liang Zhou, Jiahao Chen, Huijuan Luo, Jihua Sun, Song Wu, Yonghua Han, Guangliang Yin, Maoshan Chen, Zujing Han, Xianxin Li, Yi Huang, Weixing Zhang, Fangjian Zhou, Tong Chen, Pingping Fa, Yong WangLiang Sun, Huimin Leng, Fenghao Sun, Yuchen Liu, Mingzhi Ye, Huanming Yang, Zhiming Cai, Yaoting Gui, Xiuqing Zhang

Research output: Contribution to journal › Article › Research › peer-review

38 Citations (Scopus)

Abstract

Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research.

Original language	English
Article number	e28223
Number of pages	11
Journal	PLoS ONE
Volume	6
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0028223
Publication status	Published - 30 Nov 2011
Externally published	Yes

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Zhu, J., Jiang, Z., Gao, F., Hu, X., Zhou, L., Chen, J., Luo, H., Sun, J., Wu, S., Han, Y., Yin, G., Chen, M., Han, Z., Li, X., Huang, Y., Zhang, W., Zhou, F., Chen, T., Fa, P., ... Zhang, X. (2011). A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer. PLoS ONE, 6(11), Article e28223. https://doi.org/10.1371/journal.pone.0028223

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title = "A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer",

abstract = "Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to {"}neurogenesis{"} and {"}cell differentiation{"} by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research.",

author = "Jialou Zhu and Zhimao Jiang and Fei Gao and Xueda Hu and Liang Zhou and Jiahao Chen and Huijuan Luo and Jihua Sun and Song Wu and Yonghua Han and Guangliang Yin and Maoshan Chen and Zujing Han and Xianxin Li and Yi Huang and Weixing Zhang and Fangjian Zhou and Tong Chen and Pingping Fa and Yong Wang and Liang Sun and Huimin Leng and Fenghao Sun and Yuchen Liu and Mingzhi Ye and Huanming Yang and Zhiming Cai and Yaoting Gui and Xiuqing Zhang",

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Zhu, J, Jiang, Z, Gao, F, Hu, X, Zhou, L, Chen, J, Luo, H, Sun, J, Wu, S, Han, Y, Yin, G, Chen, M, Han, Z, Li, X, Huang, Y, Zhang, W, Zhou, F, Chen, T, Fa, P, Wang, Y, Sun, L, Leng, H, Sun, F, Liu, Y, Ye, M, Yang, H, Cai, Z, Gui, Y & Zhang, X 2011, 'A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer', PLoS ONE, vol. 6, no. 11, e28223. https://doi.org/10.1371/journal.pone.0028223

TY - JOUR

T1 - A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer

AU - Zhu, Jialou

AU - Jiang, Zhimao

AU - Gao, Fei

AU - Hu, Xueda

AU - Zhou, Liang

AU - Chen, Jiahao

AU - Luo, Huijuan

AU - Sun, Jihua

AU - Wu, Song

AU - Han, Yonghua

AU - Yin, Guangliang

AU - Chen, Maoshan

AU - Han, Zujing

AU - Li, Xianxin

AU - Huang, Yi

AU - Zhang, Weixing

AU - Zhou, Fangjian

AU - Chen, Tong

AU - Fa, Pingping

AU - Wang, Yong

AU - Sun, Liang

AU - Leng, Huimin

AU - Sun, Fenghao

AU - Liu, Yuchen

AU - Ye, Mingzhi

AU - Yang, Huanming

AU - Cai, Zhiming

AU - Gui, Yaoting

AU - Zhang, Xiuqing

PY - 2011/11/30

Y1 - 2011/11/30

N2 - Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research.

AB - Background: DNA methylation aberration and microRNA (miRNA) deregulation have been observed in many types of cancers. A systematic study of methylome and transcriptome in bladder urothelial carcinoma has never been reported. Methodology/Principal Findings: The DNA methylation was profiled by modified methylation-specific digital karyotyping (MMSDK) and the expression of mRNAs and miRNAs was analyzed by digital gene expression (DGE) sequencing in tumors and matched normal adjacent tissues obtained from 9 bladder urothelial carcinoma patients. We found that a set of significantly enriched pathways disrupted in bladder urothelial carcinoma primarily related to "neurogenesis" and "cell differentiation" by integrated analysis of -omics data. Furthermore, we identified an intriguing collection of cancer-related genes that were deregulated at the levels of DNA methylation and mRNA expression, and we validated several of these genes (HIC1, SLIT2, RASAL1, and KRT17) by Bisulfite Sequencing PCR and Reverse Transcription qPCR in a panel of 33 bladder cancer samples. Conclusions/Significance: We characterized the profiles between methylome and transcriptome in bladder urothelial carcinoma, identified a set of significantly enriched key pathways, and screened four aberrantly methylated and expressed genes. Conclusively, our findings shed light on a new avenue for basic bladder cancer research.

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U2 - 10.1371/journal.pone.0028223

DO - 10.1371/journal.pone.0028223

M3 - Article

C2 - 22140553

AN - SCOPUS:82355170973

SN - 1932-6203

VL - 6

JO - PLoS ONE

JF - PLoS ONE

IS - 11

M1 - e28223

ER -

A systematic analysis on DNA methylation and the expression of both mRNA and microRNA in bladder cancer

Abstract

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