Genome-Wide Analysis of Dna Methylation and Their Associations With Long Noncoding Rna/Mrna Expression in Non-Small-Cell Lung Cancer

Abstract

Aim: The goal of this study is to identify differentially methylated (DM) loci associated with long noncoding RNA (lncRNA)/mRNA expression in non-small-cell lung cancer (NSCLC). Materials & methods: Microarrays were used to interrogate genome-wide methylation and expression of lncRNA/mRNA in NSCLC. Results: We identified 113,644 DM loci between tumors and adjacent tissues. Among them, 26,310 DM loci were associated with 1685 differentially expressed genes, and 839 genes had significant correlations between methylation and expression, of which 26 hypermethylated loci in transcription start site 200 were correlated with low gene expression. We validated the correlations between methylation and expression in five genes (CDO1, C2orf40, SCARF1, ZFP106 and IFFO1) using pyrosequencing and quantitative polymerase chain reaction. We also found significant correlations between lncRNAs and mRNAs, and validated four of the correlations with quantitative polymerase chain reaction. Conclusion: Integrated analysis of genome-wide DNA methylation and lncRNA/mRNA expression allows us to identify new DM loci-correlated with gene expression in NSCLC.

Keywords::

• genome-wide methylation
• long noncoding RNA
• lung cancer
• microarray expression

B Qian, H Yu, N Feng conceived the study; N Feng, Y Wang, M Zheng, X Yu, H Lin, R Ma performed experiments; N Feng, O Shi, L Garmire analyzed the data; X Zheng, M Gao provided clinical material and data; N Feng, H Yu wrote the manuscript. All authors read and approved the manuscript.

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (Grant No.81573231), Natural Science Foundation of Shanghai (Grant No. 15ZR1424400) and Translational Medicine Foundation of SJTU medical college (Grant No. 15ZH1001). 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 authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant No.81573231), Natural Science Foundation of Shanghai (Grant No. 15ZR1424400) and Translational Medicine Foundation of SJTU medical college (Grant No. 15ZH1001). 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.