APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells
APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells
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APOBEC3B 和 IL-6 在肝细胞癌细胞中形成正反馈环
DOI：
10.1007/s11427-016-9058-6
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发表时间：
2017-06-01
影响因子：
9.1
通讯作者：
Yang, Yong
中科院分区：
文献类型：
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作者：
Li, Shuran;Bao, Xueyang;Yang, Yong
APOBEC3 蛋白家族（一种 DNA 胞苷脱氨酶）在多种肿瘤中表达上调。然而，肝细胞癌 (HCC) 与 APOBEC3B (A3B) 之间的关系仍不清楚。已证实白细胞介素6（IL-6）对HCC的发生具有显着影响。在这里，我们报道了 HepG2 细胞中 A3B 显着上调 IL-6 的表达。 A3B通过重新定位HuR诱导IL-6表达，增强IL-6 mRNA的稳定性。进一步分析表明，IL-6还通过JAK1/STAT3信号通路增加A3B的表达，形成正反馈，维持A3B和IL-6的持续表达，从而促进长期未消退的炎症。总的来说，这些发现表明 A3B 对于 HCC 的肿瘤发生至关重要，并且是预防性干预的潜在目标。
APOBEC3 protein families, a DNA cytidine deaminase, were up-regulated in multiple tumors. However, the relationship between Hepatocellular carcinoma (HCC) and APOBEC3B (A3B) remains unknown. It has been confirmed that interleukin-6 (IL-6) has significant impacts on oncogenesis of HCC. Here, we reported that the expression of IL-6 was substantially up-regulated by A3B in HepG2 cells. A3B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3B through JAK1/STAT3 signaling pathway, which formed a positive feedback to maintain the continuous expression of A3B and IL-6, and thereby promoted the prolonged non-resolving inflammation. Collectively, these findings suggest that A3B is essential for oncogenesis of HCC, and is a potential target for preventive intervention.