MicroRNA-193a-5p Regulates the Synthesis of Polyunsaturated Fatty Acids by Targeting Fatty Acid Desaturase 1 (FADS1) in Bovine Mammary Epithelial Cells

Abstract

Cardiovascular diseases (CVDs) are seriously threatening to human life and health. Polyunsaturated fatty acids (PUFAs) are known for their role in preventing CVDs. It is beneficial to population health to promote the content of PUFAs in bovine milk. In recent years, limited research based on molecular mechanisms has focused on this field. The biological roles of numerous microRNAs (miRNAs) remain unknown. In this study, a promising and negatively correlated pair of the miRNA (miRNA-193a-5p) and a fatty acid desaturase 1 (FADS1) gene are identified and screened to explore whether they are potential factors of PUFAs’ synthesis in bovine milk. The targeted relationship between miRNA-193a-5p and FADS1 in bovine mammary epithelial cells (BMECs) is demonstrated by dual luciferase reporter assays. qRT-PCR and western blot assays indicate that both the expression of mRNA and the protein FADS1 show a negative correlation with miRNA-193a-5p expression in BMECs. Also, miR-193a-5p expression is positively correlated with the expression of genes associated with milk fatty acid metabolism, including ELOVL fatty acid elongase 6 (ELOVL6) and diacylglycerol O-acyltransferase 2 (DGAT2). The expression of fatty acid desaturase 2 (FADS2) is negatively correlated with miR-193a-5p expression in BMECs. The contents of triglycerides (TAG), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) have a significant positive correlation with the expression of FADS1 and a significant negative correlation with the expression of miR-193a-5p in BMECs. For the first time, this study confirms that miRNA-193a-5p regulates PUFAs metabolism in BMECs by targeting FADS1, indicating that miRNA-193a-5p and FADS1 are underlying factors that improve PUFAs content in bovine milk.

The Role of microRNAs in the Mammary Gland Development, Health, and Function of Cattle, Goats, and Sheep

“…Recently, the ability of miR-485 to regulate the synthesis of triglycerides, non-esterified fatty acids, and cholesterol in the mammary epithelial cells of cows, by inhibiting the expression of the DTX4 gene, which is a PPAR-γ transcription factor, was observed [141]. Additionally, recently demonstrated the regulation of the synthesis of polyunsaturated fatty acids by miR-193a-5p through the modulation of fatty acid desaturase 1 (FADS1), leading the authors to conclude a role for this miRNA in regulating the amount of milk fatty acids in the epithelial cells of the mammary glands of cattle [142].…”

Regulation of long-chain polyunsaturated fatty acid biosynthesis in teleost fish

“…Overall, studies on the roles of miRNA in the regulation of LC-PUFA biosynthesis have only been reported in S. canaliculatus, but not yet in other fish species or other vertebrates, except for miR-193a-5p that was shown to regulate LC-PUFA biosynthesis by targeting FADS1 in bovine mammary epithelial cells [172]. As described above, individual miRNA or clusters regulated rabbitfish LC-PUFA biosynthesis by targeting fads2, elovl or TF-encoding genes.…”

MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR

“…The miR-204-5p and miR-211 were found to coordinately inhibit the content of α-S1 casein (CSN1S1) (4). The effect of other miRNAs on MECs has also been reported, including miR-193a-5p (5), miR-128 (6), miR-106b (7), miR-221 (8), miR-16a (9), and miR-26a/b (10). However, these studies have been focused on dairy cows and dairy goats.…”