Triclosan down-regulates fatty acid synthase through microRNAs in HepG2 cells

Abstract

Triclosan is a promising candidate of fatty acid synthase (FASN) inhibitor by blocking FASN activity, but its effect on FASN expression and the underling epigenetic mechanism remain elusive. In this study, the effect of triclosan on FASN mRNA and protein expressions in human HepG2 cells and the regulatory role of microRNAs (miRNAs) in the downregulation of FASN induced by triclosan were explored through experiments and bioinformatics analysis. The results showed that triclosan not only directly inhibited FASN activity, but also significantly decreased FASN mRNA and protein levels in human liver HepG2 cells. Nine miRNAs targeting FASN mRNA degradation were identified by miRNA prediction tools, and the expression levels of these nine miRNAs were then detected by real-time quantitative PCR. Triclosan significantly increased the expressions of the six miRNAs, namely miR-15a, miR-107, miR-195, miR-424, miR-497 and miR-503, leading to the downregulation of FASN. Further investigation revealed that the six triclosan-upregulated miRNAs played an important regulatory role in lipid metabolism and cell cycle by gene ontology annotations and pathway analysis. Consistent with the results of bioinformatics analyses, triclosan significantly reduced the intracellular lipid content by triglyceride assay, oil red O, BODIPY 493/503 and Nile Red staining, thereby inhibiting the growth of HepG2 cells through apoptosis. Taken together, our study reveals that triclosan downregulates FASN expression through a variety of miRNAs, providing new insight for triclosan as a FASN inhibitor candidate to regulate lipid metabolism in human hepatoma cells.

Keywords: Fatty acid synthase; HepG2 cells; Lipid metabolism; Triclosan; microRNA.