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IL-10 regulates the malignancy of hemangioma-derived endothelial cells via regulation of PCNA.
Archives of Biochemistry and Biophysics ( IF 3.9 ) Pub Date : 2020-05-13 , DOI: 10.1016/j.abb.2020.108404
Zhaofan Zeng 1 , Hao Chen 1 , Junhong Cai 2 , Yanjing Huang 3 , Jie Yue 4
Affiliation  

Hemangioma (HA) is the most common benign tumor and formed by the proliferating endothelial cells of blood vessels. Interleukins (ILs) have been reported to be critical for HA progression. Our present study found that the expression of IL-10 was decreased in HA cells and tissues as compared to their corresponding controls. Treatment with recombinant IL-10 (rIL-10) can suppress the proliferation of HA cells via suppression of proliferating cell nuclear antigen (PCNA), while over expression of PCNA can attenuate rIL-10-inhibited cell proliferation. Further, rIL-10 can decrease the promoter activity and mRNA stability of PCNA in HA cells. Mechanistically, rIL-10 can increase expression of miR-27b-3p to decrease mRNA stability of PCNA, while down regulation of YY1 is involved in rIL-10 suppressed transcription of PCNA. Collectively, IL-10 can suppress the expression of PCNA via miR-27b-3p mediated suppression of mRNA stability and YY1 mediated down regulation of transcription. It suggested that rIL-10 might be a potential therapeutic approach for HA development and progression.

中文翻译:

IL-10通过调节PCNA来调节血管瘤来源的内皮细胞的恶性肿瘤。

血管瘤(HA)是最常见的良性肿瘤,由血管内皮细胞增殖形成。已经报道白介素(ILs)对于HA进展至关重要。我们目前的研究发现,与相应的对照相比,HA细胞和组织中IL-10的表达降低。重组IL-10(rIL-10)处理可通过抑制增殖细胞核抗原(PCNA)抑制HA细胞的增殖,而PCNA的过度表达可减弱rIL-10抑制的细胞增殖。此外,rIL-10可以降低HA细胞中PCNA的启动子活性和mRNA稳定性。从机理上讲,rIL-10可以增加miR-27b-3p的表达,从而降低PCNA的mRNA稳定性,而YY1的下调与rIL-10抑制PCNA的转录有关。总的来说,IL-10可以通过miR-27b-3p介导的mRNA稳定性抑制和YY1介导的转录下调来抑制PCNA的表达。它提示rIL-10可能是HA发生和发展的潜在治疗方法。
更新日期:2020-05-13
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