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A Novel Y-Specific Long Non-Coding RNA Associated with Cellular Lipid Accumulation in HepG2 cells and Atherosclerosis-related Genes

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posted on 08.08.2018, 14:55 by Elsa Molina, Guat S. Chew, Stephen A. Myers, Elyse M. Clarence, James M. Eales, Maciej Tomaszewski, Fadi J. Charchar
There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.

Funding

We thank Brendan Yee and Rita Rozmarynowycz (Affymetrix®) for their advice with RNA FISH and for providing reagents. We also thank Fahima Ahmady for her help as Laboratory Technical Officer. This work was supported by funding from an International Postgraduate Research Scholarship at Federation University Australia, the Collaborative Research Network (CRN), and the National Health and Medical Research Council of Australia (Project Grant GNT1009490).

History

Citation

Scientific Reports, 2017, 7:16710

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

Scientific Reports

Publisher

Nature Publishing Group

issn

2045-2322

eissn

2045-2322

Acceptance date

22/11/2017

Copyright date

2017

Available date

08/08/2018

Publisher version

https://www.nature.com/articles/s41598-017-17165-9

Notes

Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-017-17165-9

Language

en

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