Abstract

Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels is associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce protein expression of their target genes and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3′-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Furthermore, we found that obese subjects have lower levels of miR-615-3p than healthy individuals. Moreover, there was a significant negative correlation between miR-615-3p and plasma lipids and apoB levels. These studies indicate that miR-615-3p negatively regulates apoB and its plasma levels could serve as a biomarker for obesity and possibly other metabolic diseases.