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Bta- miR-484通过靶向MAP3K9抑制JNK信号通路来调节牛肌内前体脂肪细胞的增殖和凋亡。

Bta-miR-484 regulates proliferation and apoptosis of bovine intramuscular preadipocytes via targeting MAP3K9 to inhibit the JNK signaling pathway.

作者信息

Ma Xinhao, Zhang Dianqi, Yang Zhimei, Sun Meijun, Mei Chugang, Zan Linsen

机构信息

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China.

College of Grassland Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, PR China; National Beef Cattle Improvement Center, Northwest A&F University, Yangling, Shaanxi 712100, PR China.

出版信息

Int J Biol Macromol. 2025 Jan;286:138082. doi: 10.1016/j.ijbiomac.2024.138082. Epub 2024 Nov 26.

Abstract

Intramuscular fat (IMF) plays a crucial role in enhancing the tenderness, flavor, and juiciness of beef, making the increase of IMF content a significant objective in beef breeding. A key factor influencing IMF levels is the number of intramuscular preadipocytes. Previous studies have indicated a correlation between bta-miR-484 and IMF content. In this study, we found that bta-miR-484 is differentially expressed during the proliferation of intramuscular preadipocytes. Our research identified that bta-miR-484 targets MAP3K9, revealing a novel mechanism for regulating both proliferation and apoptosis via the JNK signaling pathway. Functional gain and loss experiments demonstrated that bta-miR-484 inhibits the transition of bovine intramuscular preadipocytes from the G0/G1 phase to the S phase, and significant increase the proportion of early apoptotic cells. Additionally, miRNA pulldown and luciferase reporter assays confirmed MAP3K9 as the target gene of bta-miR-484. Furthermore, rescue experiments indicated that bta-miR-484 mediates its effects on proliferation and apoptosis through the MAP3K9/JNK/CCND1 and MAP3K9/JNK/BCL2 axes. These findings suggest that bta-miR-484 is a non-coding RNA that inhibits the proliferation and promotes the apoptosis of intramuscular preadipocytes, indicating that treatment with bta-miR-484 may offers a novel strategy for enhancing IMF content.

摘要

肌内脂肪(IMF)在提高牛肉的嫩度、风味和多汁性方面起着至关重要的作用,因此提高IMF含量成为肉牛育种的一个重要目标。影响IMF水平的一个关键因素是肌内前脂肪细胞的数量。先前的研究表明bta-miR-484与IMF含量之间存在相关性。在本研究中,我们发现bta-miR-484在肌内前脂肪细胞增殖过程中存在差异表达。我们的研究确定bta-miR-484靶向MAP3K9,揭示了一种通过JNK信号通路调节增殖和凋亡的新机制。功能获得和缺失实验表明,bta-miR-484抑制牛肌内前脂肪细胞从G0/G1期向S期的转变,并显著增加早期凋亡细胞的比例。此外,miRNA下拉和荧光素酶报告基因检测证实MAP3K9是bta-miR-484的靶基因。此外,拯救实验表明,bta-miR-484通过MAP3K9/JNK/CCND1和MAP3K9/JNK/BCL2轴介导其对增殖和凋亡的影响。这些发现表明,bta-miR-484是一种抑制肌内前脂肪细胞增殖并促进其凋亡的非编码RNA,这表明用bta-miR-484处理可能为提高IMF含量提供一种新策略。

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