Journal
LIFE SCIENCES
Volume 264, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118633
Keywords
Hypercholesterolemia; microRNA-128-3p; INSIG1; LDLR; CYP7A1
Funding
- Department of Biotechnology, New Delhi, India [GAP000110, BT/PR16472/BlD/7/629/2016]
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The study demonstrates that inhibition of miR-128-3p can lower serum cholesterol levels, increase the clearance of cholesterol by SR-B1 and LDLR, and promote the catabolism of cholesterol by CYP7A1, highlighting its significant therapeutic implications in reversing hypercholesterolemia.
Aims: Hypercholesterolemia remains a critical risk factor for cardiovascular diseases and there is an urgent need to develop effective alternative therapeutics. Herein, we investigated the effects of miR-128-3p inhibition on serum cholesterol levels using a hypercholesterolemic mouse model. Materials and methods: Five injections of anti-miR-128-3p (AM-128) treatment were given, and the cholesterol profile in serum and liver was quantified. We validated the underlying gene network using qRT-PCR, western blotting, ELISA, and dual luciferase assays. Key findings: AM-128 treatment inhibits cholesterol biosynthesis by upregulating INSIG1 and downregulating HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) expression. The serum cholesterol clearance by SR-B1 (scavenger receptor class B member 1) and LDLR (low density lipoprotein receptors) was also increased. Furthermore, the catabolism of cholesterol by CYP7A1 (cytochrome P450 family 7 subfamily A member 1) was increased. Significance: Our results confirmed a critical role of miR-128-3p inhibition in lowering serum cholesterol and suggest its potential therapeutic implications in reversing hypercholesterolemia.
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