MiR-130a in the adipogenesis of human SGBS preadipocytes and its susceptibility to androgen regulation

MiR-130a in the adipogenesis of human SGBS preadipocytes and its susceptibility to androgen regulation
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DOI:
10.1080/21623945.2020.1750256
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发表时间:
2020-01-01
期刊:
影响因子:
3.3
通讯作者:
Behre, Hermann M.
Behre, Hermann M.
中科院分区:
生物学4区
文献类型:
--
作者:
Greither, Thomas;Wenzel, Carina;Behre, Hermann M.

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目的:脂肪发生是指未分化的间充质干细胞分化成成熟脂肪细胞的过程。分化可以被雄激素抑制,尽管关于这种抑制的细胞内效应的知识很少。最近,在这种情况下,雄激素调节的microrna被发现是有趣的候选者。在本研究中,我们分析了miR-130a和miR-301在人SGBS前脂肪细胞脂肪形成中的作用,以及它们是否容易受到雄激素调节。材料与方法:采用qPCR方法检测雄激素刺激和非雄激素刺激下成脂分化过程中microRNA的表达。通过目标数据库搜索确定miR-130a和miR-301的推定靶基因,并在荧光素酶报告基因试验中进行验证。结果:与第0天相比,miR-130a和miR-301在成脂分化的第3天和第5天均显著下调。在雄激素刺激下,miR-130a在脂肪形成持续到第14天的7天后被检测到显著上调,而miR-301直到第14天才发生显著变化。荧光素酶报告基因检测显示雄激素受体(AR)、脂联素(ADIPOQ)和肿瘤坏死因子α (TNF α)是miR-130a的靶基因。结论:miR-130a是雄激素调控的microRNA,在脂肪形成早期下调,通过调节AR和ADIPOQ翻译发挥作用。这些数据可能有助于识别与雄激素介导的脂肪生成抑制相关的新信号通路。
Objectives: Adipogenesis is the differentiation process generating mature adipocytes from undifferentiated mesenchymal stem cells. The differentiation can be inhibited by androgens, although knowledge about intracellular effectors of this inhibition is scarce. Recently, androgen-regulated microRNAs were detected as interesting candidates in this context. In this study, we analyse the role of miR-130a and miR-301 in the adipogenesis of human SGBS preadipocytes and whether they are prone to androgen regulation. Materials and Methods: microRNA expression during adipogenic differentiation with or without androgen stimulation was measured by qPCR. Putative target genes of miR-130a and miR-301 were identified by target database search and validated in luciferase reporter assays. Results: miR-130a and miR-301 are both significantly downregulated on day 3 and day 5 of adipogenic differentiation in comparison to day 0. Under androgen stimulation, a significant upregulation of miR-130a was detected after 7 days of adipogenesis lasting to day 14, while miR-301 did not change significantly until day 14. Luciferase reporter assays revealed the androgen receptor (AR), adiponectin (ADIPOQ) and tumour necrosis factor alpha (TNF alpha) as miR-130a target genes. Conclusions: miR-130a is an androgen-regulated microRNA that is downregulated during the early phase of adipogenesis and exerts its functions by regulating AR and ADIPOQ translation. These data may help to identify new signalling pathways associated with the androgen-mediated inhibition of adipogenesis.