Poster abstracts

Poster number 59 submitted by Joseph Iacona

miR-146a directly regulates expression of 5-lipoxygenase activating protein (FLAP) in lung cancer cells

Joseph R. Iacona (Microbiology, Biochemistry and Molecular Genetics, Rutgers Biomedical and Health Sciences-Newark, NJ), Nicholas J. Monteleone (Microbiology, Biochemistry and Molecular Genetics, Rutgers Biomedical and Health Sciences-Newark, NJ), Carol S. Lutz (Microbiology, Biochemistry and Molecular Genetics, Rutgers Biomedical and Health Sciences-Newark, NJ )

Abstract:
Arachidonic acid can be converted into prostaglandins (PGs) or leukotrienes (LTs) by cyclooxygenase (COX-1 and COX-2) or 5-lipoxygenase (5-LO) enzyme activity, respectively. PGs and LTs are lipid signaling molecules that have been implicated in various diseases, including multiple cancers. 5-LO and its activating protein (FLAP) work together in the first conversion step of LT production. Previous work has suggested a role for 5-LO and FLAP in cancer development and progression. MicroRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression at the post-transcriptional level. Several studies have shown that both 5-LO and FLAP expression are controlled in this manner. Here, we show that FLAP protein is overexpressed in lung cancer cells compared to normal lung cells. One miRNA in particular, miR-146a, is predicted to target FLAP. Transfection of synthetic miR-146a in lung cancer cells can repress endogenous FLAP mRNA and protein expression, and reporter assays indicate this regulation occurs through a direct interaction between miR-146a and the FLAP 3ʼ UTR. Intriguingly, miR-146a can also repress endogenous 5-LO mRNA and protein expression, though in an indirect manner. This concerted downregulation of 5-LO and FLAP also results in decreased cancer cell LTB4 production. This study and previous work from our lab suggest miR- 146a can regulate both PG and LT production in lung cancer cells by directly targeting the 3ʼ UTRs of COX-2 and FLAP.

Keywords: miRNA, gene expression, regulation