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15,16-dihydrotanshinone I inhibits EOMA cells proliferation by interfering in posttranscriptional processing of hypoxia-inducible factor 1
International Journal of Medical Sciences ( IF 3.2 ) Pub Date : 2021-7-11 , DOI: 10.7150/ijms.60774
Peiwen Duan 1, 2 , Yingying Huang 1, 3 , Kai Chen 1, 2 , Cheng Cheng 1, 2 , Zhixiang Wu 1, 2 , Yeming Wu 1, 2
Affiliation  

Infantile hemangioma (IH), which threatens the physical and mental health of patients, is the most common benign tumor in infants. Previously, we found that 15,16-dihydrotanshinone I (DHTS) was significantly more effective at inhibiting hemangioma proliferation in vitro and in vivo than the first-line treatment propranolol. To investigate the underlying mechanism of DHTS, we used EOMA cells as a model to study the effect of DHTS. We compared the transcriptomes of control and DHTS-treated EOMA cells. In total, 2462 differentially expressed genes were detected between the groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed downregulated activity of the hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway in EOMA cells following treatment with DHTS. Thus, we investigated HIF-1α expression at protein and mRNA levels. Our results revealed that DHTS downregulated HIF-1α expression by interfering in its posttranscriptional processing, and the RNA-binding protein HuR participated in this mechanism. Our findings provide a basis for clinical transformation of DHTS and insight into pathogenic mechanisms involved in IH./n

中文翻译:

15,16-二氢丹参酮 I 通过干扰缺氧诱导因子 1 的转录后加工抑制 EOMA 细胞增殖

婴幼儿血管瘤(IH)威胁患者身心健康,是婴幼儿最常见的良性肿瘤。此前,我们发现 15,16-二氢丹参酮 I (DHTS) 在体外和体内抑制血管瘤增殖方面比一线治疗普萘洛尔更有效。为了研究 DHTS 的潜在机制,我们使用 EOMA 细胞作为模型来研究 DHTS 的作用。我们比较了对照和 DHTS 处理的 EOMA 细胞的转录组。各组间共检测到2462个差异表达基因。京都基因百科全书和基因组通路分析揭示了 DHTS 处理后 EOMA 细胞中缺氧诱导因子 1 α (HIF-1α) 信号通路的活性下调。因此,我们研究了蛋白质和 mRNA 水平的 HIF-1α 表达。我们的研究结果表明,DHTS 通过干扰其转录后加工来下调 HIF-1α 的表达,并且 RNA 结合蛋白 HuR 参与了这一机制。我们的研究结果为 DHTS 的临床转化和深入了解 IH 的致病机制提供了基础。/n
更新日期:2021-09-08
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