State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, 211198, China.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
Sci China Life Sci. 2017 Jun;60(6):617-626. doi: 10.1007/s11427-016-9058-6. Epub 2017 May 29.
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.
APOBEC3 蛋白家族是一种 DNA 胞嘧啶脱氨酶,在多种肿瘤中上调。然而,肝癌(HCC)与 APOBEC3B(A3B)之间的关系尚不清楚。已经证实白细胞介素 6(IL-6)对 HCC 的发生有显著影响。在这里,我们报道 A3B 在 HepG2 细胞中显著上调了 IL-6 的表达。A3B 通过将 HuR 重定位来增强 IL-6 mRNA 的稳定性,从而诱导 IL-6 的表达。进一步的分析表明,IL-6 还通过 JAK1/STAT3 信号通路增加了 A3B 的表达,形成了正反馈,从而维持 A3B 和 IL-6 的持续表达,进而促进了长期非解决性炎症。总之,这些发现表明 A3B 是 HCC 发生的关键因素,是预防干预的潜在靶点。