PLoS ONE (2011-01-01)

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
https://doi.org/10.1371/journal.pone.0028223
Journal volume & issue
Vol. 6, no. 11
p. e28223

Abstract

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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.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.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.