Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2019 Oct 31;9(1):15787.
doi: 10.1038/s41598-019-51948-6.

The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing

Gabriel N Valbuena  1 , Sophia Apostolidou  2 , Rhiannon Roberts  2 , Julie Barnes  3 , Wendy Alderton  3   4 , Lauren Harper  5 , Ian Jacobs  2   6 , Usha Menon  2 , Hector C Keun  7
Affiliations
Randomized Controlled Trial

The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing

Gabriel N Valbuena et al. Sci Rep. .

Abstract

Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Distributions of study set demographic information. (A) age at sampling, (B) time to centrifugation, (C) BMI at recruitment, (D) Regional Centre of collection for our study set, (E) time difference between successive samples, and (F) time from first to last sample.
Figure 2
Figure 2
Abundance of miRNAs in circulation. (A) The top 20 miRNAs by percentage of total circulating miRNA. (B) Mean microRNA counts per million (cpm) in circulation, ordered by magnitude. (C) Cumulative fraction of total microRNAs for the top 100 microRNAs by abundance. (D) Cumulative distribution of miRNA detection rates at certain cpm thresholds.
Figure 3
Figure 3
Confounding effects of age, BMI, regional centre, and time to centrifugation. Variance explained (R2) against p-values corrected for multiple testing for (A) age, (B) BMI at study enrollment, (C) regional centre of collection, and (D) time to centrifugation.
Figure 4
Figure 4
Intra-class correlation coefficients (ICCs) for consistently detected circulating miRNAs. (A) Distribution of ICCs for consistently detected miRNAs, with a median ICC of 0.36 shown in red. (B) ICCs vs. read counts per million.
Figure 5
Figure 5
Comparison of ICCs calculated using total depth-normalized data compared to trimmed mean of m (TMM)-normalized data. (A) Distributions of ICCs and (B) scatter plot of ICCs for each miRNA of total depth-normalized data (as reads per million, RPM) and TMM- normalized data.
Figure 6
Figure 6
Comparison of ICCs from the longitudinal study carried out by Keller et al. (2017) and our own study. (A) Distributions of ICCs and (B) scatter plot comparing ICCs for 113 miRNAs detected in both studies.
Figure 7
Figure 7
A cluster of miRNAs with ICCs above 0.5 can be found on the long arm of chromosome 14.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33. doi: 10.1016/j.cell.2009.01.002. - DOI - PMC - PubMed
    1. Baek D, et al. The impact of microRNAs on protein output. Nature. 2008;455(7209):64–71. doi: 10.1038/nature07242. - DOI - PMC - PubMed
    1. Carleton M, Cleary MA, Linsley PS. MicroRNAs and cell cycle regulation. Cell Cycle. 2007;6(17):2127–32. doi: 10.4161/cc.6.17.4641. - DOI - PubMed
    1. Jovanovic M, Hengartner MO. miRNAs and apoptosis: RNAs to die for. Oncogene. 2006;25(46):6176–87. doi: 10.1038/sj.onc.1209912. - DOI - PubMed
    1. Koufaris C, et al. Systematic integration of molecular profiles identifies miR-22 as a regulator of lipid and folate metabolism in breast cancer cells. Oncogene. 2016;35(21):2766–76. doi: 10.1038/onc.2015.333. - DOI - PubMed

Publication types

MeSH terms