2017 Cardiovascular Research Day Abstract Book

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CHROME: a Long Non-coding RNA that Regulates Cholesterol Homeostasis
Kathryn Moore, PhD 1
1Medicine, New York University
Faculty
Thousands of long non-coding RNAs (lncRNAs) have been identified in the human genome, many of
which are not conserved in lower mammals. The majority of these lncRNAs remain functionally
uncharacterized and may have important implications in human physiology and disease. We
identified a primate-specific lncRNA, CHROME, which is increased in the plasma and atherosclerotic
plaques of individuals with coronary artery disease compared to healthy controls. Using gain- and
loss-of-function approaches, we show that CHROME functions as a competing endogenous RNA of
microRNAs (miRNAs) that repress cellular cholesterol efflux and plasma high density lipoproteins
(HDL) levels, and regulates the concentration and biological functions of these miRNAs. CHROME
knockdown in primary hepatocytes increases levels of its miRNA binding partners, thereby
reducing expression of their target gene networks, hepatic cholesterol and phospholipid efflux, and
the formation of nascent HDL particles. Consistent with these findings, hepatic levels of CHROME
are positively correlated with plasma levels of HDL cholesterol in healthy individuals. Collectively,
our findings identify CHROME as a central component of the non-coding RNA circuitry controlling
cholesterol homeostasis in humans.
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