miR-125a inhibits porcine preadipocytes differentiation by targeting ERRα

miR-125a inhibits porcine preadipocytes differentiation by targeting ERRα
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DOI:
10.1007/s11010-014-2121-4
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发表时间:
2014-10-01
影响因子:
4.3
通讯作者:
Yang, Gong-she
Yang, Gong-she
中科院分区:
生物学3区
文献类型:
--
作者:
Ji, Hong-lei;Song, Cheng-Chuang;Yang, Gong-she

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MicroRNA是一个小的非编码RNA家族,以序列特异性方式调节基因表达。雌激素相关受体α(ERR α)是一种孤儿核受体,在脂肪细胞分化中起重要作用。我们之前的Solexa测序结果表明miR-125 a在成年猪背膘中的高表达。在这项研究中,我们预测并实验验证了ERR α作为miR-125 a的靶点。为了探索miR-125 a在猪前脂肪细胞分化中的作用,分别使用miRNA agomir和miR 125 a进行miR-125 a过表达或敲低。我们的研究结果表明,过表达miR-125 a可以显著降低脂肪形成标志物PPAR γ、LPL和aP 2及其靶基因ERR α的mRNA表达。Western blotting显示aP 2和ERR α蛋白水平也显著下调。miR-125 a的过表达也导致脂质积累的显著减少,这通过油红O染色检测。相反,我们观察到在miR-125 a抑制后促进猪前脂肪细胞的分化。本研究首次证实miR-125 a通过靶向ERR α抑制猪前脂肪细胞分化,为猪肉品质改良和肥胖控制提供了新的思路。
MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. Estrogen-related receptor alpha (ERR alpha) is an orphan nuclear receptor which plays an important role in adipocyte differentiation. Our previous Solexa sequencing results indicated a high expression of miR-125a in adult pig backfat. In this study, we predicated and experimentally validated ERR alpha as a target of miR-125a. To explore the role of miR-125a in porcine preadipocytes differentiation, miRNA agomir and antagomir were used to perform miR-125a overexpression or knockdown, respectively. Our results showed that overexpression of miR-125a could dramatically reduce the mRNA expression of adipogenic markers PPAR gamma, LPL, and aP2, as well as its target gene ERR alpha. Western blotting showed the protein level of aP2 and ERR alpha was also significantly down-regulated. The overexpression of miR-125a also led to a notable reduction in lipid accumulation which was detected by Oil Red O staining. In contrast, we observed promoted differentiation of porcine preadipocytes upon miR-125a inhibition. In conclusion, we verified miR-125a inhibits porcine preadipocytes differentiation through targeting ERR alpha for the first time, which may provide new insights in pork quality improvement and obesity control.