4.7 Article

APOBEC3B and IL-6 form a positive feedback loop in hepatocellular carcinoma cells

Journal

SCIENCE CHINA-LIFE SCIENCES
Volume 60, Issue 6, Pages 617-626

Publisher

SCIENCE PRESS
DOI: 10.1007/s11427-016-9058-6

Keywords

APOBEC3B; interleukin-6; hepatitis; hepatocellular carcinoma; HuR

Categories

Funding

  1. National Natural Science Foundation of China [91529304, 81502407, 81473230, 81273547, 81403020, 91129731]
  2. Jiangsu Province Natural Science Foundation of China [BK2014666]
  3. Central College Fund [ZJ14020]

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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.

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