MicroRNA 140 Promotes Expression of Long Noncoding RNA NEAT1 in Adipogenesis
MicroRNA 140 Promotes Expression of Long Noncoding RNA NEAT1 in Adipogenesis
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DOI：
10.1128/mcb.00702-15
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发表时间：
2016-01-01
影响因子：
5.3
通讯作者：
Zhou, Qun
中科院分区：
文献类型：
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作者：
Gernapudi, Ramkishore;Wolfson, Benjamin;Zhou, Qun
超过40%的美国人口患有临床肥胖症和代谢综合征，绝经后雌激素受体阳性乳腺癌的风险增加。脂肪细胞是脂肪组织的主要组成部分，由前体间充质干细胞向成脂细胞分化而成。虽然脂肪形成的主要分子途径已被了解，但对参与脂肪形成的非编码RNA信号网络知之甚少。利用从野生型和microRNA140(miR-140)基因敲除小鼠分离的脂肪细胞来源的干细胞(ADSCs)，我们鉴定了一个新的miR-140/长非编码RNA(LncRNA)NEAT1信号网络，这是脂肪形成所必需的。MIR-140基因敲除的ADSC显著降低了与NEAT1表达下调相关的成脂能力。我们在NEAT1中发现了miR-140结合位点，并发现细胞核中成熟的miR-140可以物理上与NEAT1相互作用，导致NEAT1表达增加。我们证明，在miR-140基因敲除的ADSCs中重新表达NEAT1足以恢复其分化能力。我们的结果揭示了一个令人兴奋的新的非编码RNA信号网络，它调控脂肪形成，是预防或治疗肥胖症的潜在新靶点。
More than 40% of the U.S. population are clinically obese and suffer from metabolic syndrome with an increased risk of postmenopausal estrogen receptor-positive breast cancer. Adipocytes are the primary component of adipose tissue and are formed through adipogenesis from precursor mesenchymal stem cells. While the major molecular pathways of adipogenesis are understood, little is known about the noncoding RNA signaling networks involved in adipogenesis. Using adipocyte-derived stem cells (ADSCs) isolated from wild-type and microRNA 140 (miR-140) knockout mice, we identify a novel miR-140/long noncoding RNA (lncRNA) NEAT1 signaling network necessary for adipogenesis. miR-140 knockout ADSCs have dramatically decreased adipogenic capabilities associated with downregulation of NEAT1 expression. We identified a miR-140 binding site in NEAT1 and found that mature miR-140 in the nucleus can physically interact with NEAT1, leading to increased NEAT1 expression. We demonstrated that reexpression of NEAT1 in miR-140 knockout ADSCs is sufficient to restore their ability to undergo differentiation. Our results reveal an exciting new noncoding RNA signaling network that regulates adipogenesis and that is a potential new target in the prevention or treatment of obesity.