A let-7/Fas double-negative feedback loop regulates human colon carcinoma cells sensitivity to Fas-related apoptosis
A let-7/Fas double-negative feedback loop regulates human colon carcinoma cells sensitivity to Fas-related apoptosis
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DOI：
10.1016/j.bbrc.2011.04.074
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发表时间：
2011-05-13
影响因子：
3.1
通讯作者：
Yang, Jia-Mei
中科院分区：
文献类型：
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作者：
Geng, Li;Zhu, Bin;Yang, Jia-Mei
干扰素-γ（IFN-γ）被认为是调节抗肿瘤反应的关键，因为它使HT 29细胞中Fas相关的凋亡敏感，但其机制尚不清楚。在目前的研究中，我们的数据表明，IFN-γ刺激和Fas激活抑制Dicer加工和let-7 microRNA生物合成，而let-7 microRNA通过直接靶向Fas mRNA强烈抑制Fas表达。因此，我们的研究结果表明Fas和let-7 microRNA在IFN-γ和Fas诱导结肠癌细胞株HT 29凋亡中形成了一个双负反馈环，这可能是抗肿瘤免疫应答的一个重要协同机制。我们还发现let-7 microRNA抑制剂增加Fas表达并使细胞对Fas相关凋亡敏感，这可能在结肠癌治疗中具有未来意义。(C)2011 Elsevier Inc. All rights reserved.
Interferon-gamma (IFN-gamma) is considered essential for the regulation of anti-tumor reactions as it sensitizes Fas-related apoptosis in HT29 cells, but the mechanism is unclear. In the current study, our data demonstrated that IFN-gamma stimulation and Fas activation suppressed Dicer processing and let-7 microRNA biogenesis, while let-7 microRNA strongly inhibited Fas expression by directly targeting Fas mRNA. Accordingly, our results indicate that Fas and let-7 microRNAs form a double-negative feedback loop in IFN-gamma and Fas induced apoptosis in colon carcinoma cell line HT29, which may be an important synergistic mechanism in anti-tumor immune response. We also found that a let-7 microRNA inhibitor increased Fas expression and sensitized cells to Fas-related apoptosis, which may have future implications in colon carcinoma therapy. (C) 2011 Elsevier Inc. All rights reserved.