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2017 Cardiovascular Research Day Abstract Book

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60<br />

CHROME: a Long Non-coding RNA that Regulates Cholesterol Homeostasis<br />

Kathryn Moore, PhD 1<br />

1Medicine, New York University<br />

Faculty<br />

Thousands of long non-coding RNAs (lncRNAs) have been identified in the human genome, many of<br />

which are not conserved in lower mammals. The majority of these lncRNAs remain functionally<br />

uncharacterized and may have important implications in human physiology and disease. We<br />

identified a primate-specific lncRNA, CHROME, which is increased in the plasma and atherosclerotic<br />

plaques of individuals with coronary artery disease compared to healthy controls. Using gain- and<br />

loss-of-function approaches, we show that CHROME functions as a competing endogenous RNA of<br />

microRNAs (miRNAs) that repress cellular cholesterol efflux and plasma high density lipoproteins<br />

(HDL) levels, and regulates the concentration and biological functions of these miRNAs. CHROME<br />

knockdown in primary hepatocytes increases levels of its miRNA binding partners, thereby<br />

reducing expression of their target gene networks, hepatic cholesterol and phospholipid efflux, and<br />

the formation of nascent HDL particles. Consistent with these findings, hepatic levels of CHROME<br />

are positively correlated with plasma levels of HDL cholesterol in healthy individuals. Collectively,<br />

our findings identify CHROME as a central component of the non-coding RNA circuitry controlling<br />

cholesterol homeostasis in humans.<br />

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