TNFα-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors

TNFα-induced up-regulation of miR-155 inhibits adipogenesis by down-regulating early adipogenic transcription factors
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DOI:
10.1016/j.bbrc.2011.09.131
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发表时间:
2011-10-28
影响因子:
3.1
通讯作者:
Wu, Jiarui
Wu, Jiarui
中科院分区:
生物学4区
文献类型:
--
作者:
Liu, Sanhong;Yang, Ying;Wu, Jiarui

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已知肿瘤坏死因子α(TNF α)抑制脂肪形成,但这种抑制的分子机制仍然难以捉摸。在本研究中,我们发现,TNF α诱导的抑制脂肪形成主要发生在3 T3-L1前脂肪细胞用TNF α处理2小时内诱导脂肪形成。我们发现TNF α处理导致3 T3-L1细胞中miR-155通过NF κ B途径上调。miR-155的这种过表达可以通过直接靶向C/EBP β和CREB的3'非翻译区(3' UTR)来抑制它们的表达。重要的是,抗miR-155减少了TNF α诱导的脂肪生成抑制,而外源性表达miR-155抑制脂肪生成。总之,这些发现揭示了TNF α在调节抗脂肪形成miRNA中的新作用。(C)2011 Elsevier Inc. All rights reserved.
Tumor necrosis factor alpha (TNF alpha) is known to inhibit adipogenesis, but the molecular mechanism of this inhibition remains elusive. In the present study, we found that TNF alpha-induced inhibition of adipogenesis mainly occurs when 3T3-L1 preadipocytes are treated with TNF alpha within 2 h induction of adipogenesis. We revealed that TNF alpha treatment results in the up-regulation of miR-155 through the NF kappa B pathway in 3T3-L1 cells. This overexpression of miR-155 may suppress the expression of C/EBP beta and CREB by directly targeting their 3' untranslated regions (3' UTRs). Importantly, anti-miR-155 reduces the TNF alpha-induced inhibition of adipogenesis, whereas exogenous expression of mir-155 inhibits adipogenesis. Taken together, these findings reveal a novel role for TNF alpha in the regulation of anti-adipogenic miRNAs. (C) 2011 Elsevier Inc. All rights reserved.