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一种小核仁 RNA,SNORD126,通过激活 PI3K-AKT 通路促进细胞和大鼠的脂肪生成。

A small nucleolar RNA, SNORD126, promotes adipogenesis in cells and rats by activating the PI3K-AKT pathway.

机构信息

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.

出版信息

J Cell Physiol. 2021 Apr;236(4):3001-3014. doi: 10.1002/jcp.30066. Epub 2020 Sep 22.

DOI:10.1002/jcp.30066
PMID:32960468
Abstract

Small nucleolar RNA (snoRNA) plays important role in various histogenesis. Whether snoRNA plays a role in adipogenesis is unknown. SNORD126 is a C/D box snoRNA. We previously demonstrated that SNORD126 promoted hepatocellular carcinoma cell growth by activating the phosphoinositide 3-kinase-protein kinase B (Akt) pathway through upregulating fibroblast growth factor receptor 2 expression. In the present study, we found that the expression of SNORD126 was downregulated in the obesity-related tissues in high-fat diet-fed rats. Overexpression of SNORD126 in 3T3-L1 cells promoted adipocytes differentiation. SNORD126 significantly increased the expression of CCAAT/enhancer-binding protein α, fatty acid-binding protein 4, peroxisome proliferative-activated receptor-γ, and the phosphorylation of Akt and p70S6K. Overexpression of SNORD126 in human adipose-derived stem cells stimulated adipogenesis and increased phosphorylation of Akt. Meanwhile, SNORD126 increased the messenger RNA and protein levels of cyclin D1 and cyclin-dependent kinase 2, which promoted mitotic clonal expansion progression during the early stage of 3T3-L1 cell differentiation. We further found that SNORD126 accelerated the growth of the groin fat pad and increased phosphorylation of Akt and p70S6K in rats. Overall, our results suggested that SNORD126 promoted adipocyte differentiation through increasing phosphorylation of Akt and p70S6K both in vitro and in vivo.

摘要

小核仁 RNA(snoRNA)在各种组织发生中发挥重要作用。snoRNA 是否在脂肪生成中起作用尚不清楚。SNORD126 是一种 C/D 盒 snoRNA。我们之前的研究表明,SNORD126 通过上调成纤维细胞生长因子受体 2 的表达来激活磷酸肌醇 3-激酶-蛋白激酶 B(Akt)通路,从而促进肝癌细胞的生长。在本研究中,我们发现 SNORD126 在高脂肪饮食喂养的大鼠肥胖相关组织中的表达下调。3T3-L1 细胞中 SNORD126 的过表达促进了脂肪细胞分化。SNORD126 显著增加了 CCAAT/增强子结合蛋白α、脂肪酸结合蛋白 4、过氧化物酶体增殖物激活受体-γ 的表达,以及 Akt 和 p70S6K 的磷酸化。人脂肪源性干细胞中 SNORD126 的过表达刺激了脂肪生成,并增加了 Akt 的磷酸化。同时,SNORD126 增加了细胞周期蛋白 D1 和细胞周期蛋白依赖性激酶 2 的信使 RNA 和蛋白水平,促进了 3T3-L1 细胞分化早期的有丝分裂克隆扩张进展。我们进一步发现 SNORD126 加速了腹股沟脂肪垫的生长,并增加了大鼠中 Akt 和 p70S6K 的磷酸化。总的来说,我们的结果表明,SNORD126 通过增加 Akt 和 p70S6K 的磷酸化,在体内和体外均促进脂肪细胞分化。

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