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. 2018 May;27(5):550-557.
doi: 10.1158/1055-9965.EPI-17-0849. Epub 2018 Feb 23.

miRNA-Processing Gene Methylation and Cancer Risk

Brian T Joyce  1 , Yinan Zheng  2   3 , Zhou Zhang  2 , Lei Liu  2   4 , Masha Kocherginsky  5 , Robert Murphy  6 , Chad J Achenbach  7 , Jonah Musa  6   8   9 , Firas Wehbe  5 , Allan Just  10 , Jincheng Shen  11 , Pantel Vokonas  12 , Joel Schwartz  13 , Andrea A Baccarelli  14 , Lifang Hou  2   4
Affiliations

miRNA-Processing Gene Methylation and Cancer Risk

Brian T Joyce et al. Cancer Epidemiol Biomarkers Prev. 2018 May.

Abstract

Background: Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNA-processing genes. Studies have found genetic alterations to miRNA-processing genes in cancer cells and human population studies. Our objective was to prospectively examine changes in DNA methylation of miRNA-processing genes and their associations with cancer risk.Methods: We examined cohort data from the Department of Veterans' Affairs Normative Aging Study. Participants were assessed every 3 to 5 years starting in 1999 through 2013 including questionnaires, medical record review, and blood collection. Blood from 686 consenting participants was analyzed using the Illumina 450K BeadChip array to measure methylation at CpG sites throughout the genome. We selected 19 genes based on a literature review, with 519 corresponding CpG sites. We then used Cox proportional hazards models to examine associations with cancer incidence, and generalized estimating equations to examine associations with cancer prevalence. Associations at false discovery rate < 0.05 were considered statistically significant.Results: Methylation of three CpGs (DROSHA: cg23230564, TNRC6B: cg06751583, and TNRC6B: cg21034183) was prospectively associated with time to cancer development (positively for cg06751583, inversely for cg23230564 and cg21034183), whereas methylation of one CpG site (DROSHA: cg16131300) was positively associated with cancer prevalence.Conclusions: DNA methylation of DROSHA, a key miRNA-processing gene, and TNRC6B may play a role in early carcinogenesis.Impact: Changes in miRNA processing may exert multiple effects on cancer development, including protecting against it via altered global miRNAs, and may be a useful early detection biomarker of cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 550-7. ©2018 AACR.

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Conflict of interest statement

Conflicts of Interest

The authors have no conflicts of interest to report.

Figures

Figure 1
Figure 1
Roles of candidate genes in miRNA biogenesis Figure 1 diagrams the involvement of each candidate gene of interest in distinct step(s) of miRNA processing both within and without of the nucleus. It also labels distinct precursor miRNA products generated up to mRNA silencing in the RNA silencing complex (RISC). Critical miRNA processing genes/steps are bolded.
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