m⁶A Rna Modification Modulates Gene Expression and Cancer-Related Pathways in Clear Cell Renal Cell Carcinoma

Abstract

Aim: To systematically profile the global m⁶A modification pattern in clear cell renal cell carcinoma (ccRCC). Methods: m⁶A modification patterns in ccRCC and normal tissues were described via m⁶A sequencing and RNA sequencing, followed by bioinformatics analysis. m⁶A-related RNAs were immunoprecipitated and validated by quantitative real-time PCR (qPCR). Results: In total, 6919 new m⁶A peaks appeared with the disappearance of 5020 peaks in ccRCC samples. The unique m⁶A-related genes in ccRCC were associated with cancer-related pathways. We identified differentially expressed mRNA transcripts with hyper-methylated or hypo-methylated m⁶A peaks in ccRCC. Conclusion: This study presented the first m⁶A transcriptome-wide map of human ccRCC, which may shed lights on possible mechanisms of m⁶A-mediated gene expression regulation.

Keywords::

• clear cell renal cell carcinoma
• m⁶A-sequencing
• modification patterns
• N⁶-methyladenosine

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0182

Author contributions

D Xue and X He designed and supervised the whole study. Y Chen performed experiments, provided statistical analysis and wrote the manuscript. C Zhou and Y Sun collected samples and clinical data, and revised the manuscript. D Xue gave final approval of the version to be published.

Acknowledgments

The authors thank the patients who contributed to this study. They thank Cloudseq Biotech, Inc. (Shanghai, China) for the m⁶A meRIP sequencing service and bioinformatics support.

Financial & competing interests disclosure

This project was supported by Jiangsu Provincial 333 Department Support project (BRA2017116) and Changzhou Municipal Science and Technology Bureau Support project (CE20175030). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was approved by the ethics committee of the hospital, and the written informed consent was obtained from all participants. All procedures performed in studies involving human participants were compliant with the ethical standards.

Additional information

Funding

This project was supported by Jiangsu Provincial 333 Department Support project (BRA2017116) and Changzhou Municipal Science and Technology Bureau Support project (CE20175030). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.