miR-145 通过靶向 FOXO1 影响牛乳腺上皮细胞中的 SERBP1 活性来调节脂肪酸代谢,Journal of Agricultural and Food Chemistry

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miR-145 通过靶向 FOXO1 影响牛乳腺上皮细胞中的 SERBP1 活性来调节脂肪酸代谢
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-05-08 , DOI: 10.1021/acs.jafc.2c09001
Ming Lyu ₁ , Fang Li ₁ , Xu Wang ₁ , Kun Xu ₁ , Shuang Sun ₂

Affiliation

MicroRNA 介导的基因调控对于脂肪酸代谢和合成的调控很重要。我们之前的研究发现miR-145在奶牛泌乳乳腺中的表达高于干奶期，但其潜在的分子机制尚不完全清楚。在这项研究中，我们研究了 miR-145 在牛乳腺上皮细胞 (BMEC) 中的潜在作用。我们发现 miR-145 的表达在哺乳期间逐渐增加。BMEC 中 CRISPR/Cas9 介导的 miR-145 敲除 (KO) 导致脂肪酸代谢相关基因的表达下调。进一步的结果表明，miR-145 KO 减少了总甘油三酯 (TAG) 和胆固醇 (TC) 的积累，并改变了细胞内脂肪酸（C16:0、C18:0 和 C18:1）的组成。反过来，miR-145 过表达具有相反的效果。生物信息学在线程序预测 miR-145 靶向 Forkhead Box O1 的 3'-UTR（FOXO1 ) 基因。随后，通过 qRT-PCR、蛋白质印迹分析和荧光素酶报告基因测定，FOXO1被确定为 miR-145 的直接靶标。此外，siRNA 介导的FOXO1沉默促进了 BMEC 中的脂肪酸代谢和 TAG 合成。此外，我们观察到FOXO1参与甾醇调节元件结合蛋白 1 ( SREBP1 ) 基因启动子的转录活性。总体而言，我们的研究结果表明，miR-145 通过靶向 FOXO1 减轻了FOXO1对SREBP1表达的抑制作用进而调节脂肪酸代谢。因此，我们的研究结果从 miRNA-mRNA 网络的角度提供了关于提高牛奶产量和质量的分子机制的有价值的信息。

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miR-145 Modulates Fatty Acid Metabolism by Targeting FOXO1 to Affect SERBP1 Activity in Bovine Mammary Epithelial Cells

MicroRNA-mediated gene regulation is important for the regulation of fatty acid metabolism and synthesis. Our previous study uncovered that the miR-145 expression is higher in the lactating mammary gland of dairy cows than in the dry-period, but the underlying molecular mechanism is incompletely understood. In this study, we have investigated the potential role of miR-145 in bovine mammary epithelial cells (BMECs). We found that the expression of miR-145 gradually increased during lactation. CRISPR/Cas9-mediated knockout (KO) of miR-145 in BMECs results in the downregulated expression of fatty acid metabolism-associated genes. Further results revealed that miR-145 KO reduced total triacylglycerol (TAG) and cholesterol (TC) accumulation and altered the composition of intracellular fatty acids (C16:0, C18:0, and C18:1). Conversely, miR-145 overexpression had the opposite effect. Bioinformatics online program predicted that miR-145 targets the 3′-UTR of the Forkhead Box O1 (FOXO1) gene. Subsequently, FOXO1 was identified as a direct target of miR-145 by qRT-PCR, Western blot analysis, and luciferase reporter assay. Furthermore, siRNA-mediated silencing of FOXO1 promoted fatty acid metabolism and TAG synthesis in BMECs. Additionally, we observed the involvement of FOXO1 in the transcriptional activity of the sterol regulatory element-binding protein 1 (SREBP1) gene promoter. Overall, our findings indicated that miR-145 relieves the inhibitory effect of FOXO1 on SREBP1 expression by targeting FOXO1 and subsequently regulating fatty acid metabolism. Thus, our results provide valuable information on the molecular mechanisms for improving milk yield and quality from the perspective of miRNA-mRNA networks.

更新日期：2023-05-08

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