The Study of stearoyl CoA desaturase 1 chemical inhibition effect on miR32 and miR616 expression, migration capability and phospholipids fatty acid composition in breast cancer cell line MDA-MB-231

Abstract

Changes in the levels of saturated (SFAs) and monounsaturated fatty acids (MUFAs) can alter a wide range of cellular mechanisms involved in carcinogenesis, such as synthesis of membrane phospholipids, proliferative capacity, and migration. The conversion of SFA to MUFA is catalyzed by thestearoyl CoA desaturase 1 (SCD1). Therefore, the inhibition of this enzyme can disrupt the aforementioned pathological processes. miR32 and miR616 are also involved in the proliferation and invasion of cancer cells. Aim: The aim of this study is to investigate the effect of SCD1 enzyme inhibition using CAY10566 inhibitor on cell membrane phospholipids fatty acid composition and cell migration capability and expression level of miR32 and miR616 in MDA-MB-231 breast cancer cell line. Methods: Cells were treated with a non-toxic dose of the inhibitor for 72 hours. After phospholipid fraction fatty acids extraction, the composition of phospholipid fatty acids was evaluated using gas-liquid chromatography. To evaluate the cells migration capability, scratch assay was performed. The expression of two miRNAs was investigated by Real time-PCR. Results: After SCD1 enzyme inhibition by CAY10566 inhibitor in the treatment group, the MUFA level in phospholipids structure decreased compared to the control group (16:1/16:0 and 18:1/18:0, P<0.0001 and p<0.032 respectively). In cell migration assay after the treatment, it was found that the cell migration capability decreased in the treatment group compared to the control (p<0.01). Evaluation of miR32 and miR616 expression level also showed that SCD1 enzyme inhibition in the treatment group causes a decrease in the expression of these two compared to the control group (p<0.0001 for both).