Inflammatory factors and activation of oncogenes both played critical roles in the development and progression of human hepatocellular carcinoma (HCC). However, the interplay between these two has not been well studied. In this study, we found that regulated by TNFα, Pim-2 proto-oncogene, serine/threonine kinase (PIM2) was highly expressed in HCC and correlated with poor prognosis (P = 0.007) as well as tumor recurrence (P = 0.014). Functional studies showed that PIM2 could enhance abilities of cell proliferation, cell motility, angiogenesis, chemo-resistance, and in vivo tumorigenicity and HCC metastasis. Mechanistic studies revealed that PIM2 could activate NF-κB signaling pathway through upregulating phosphorylation level of RIPK2. Interestingly, TNFα treatment could induce the expression of PIM2, and overexpression of PIM2 could in turn upregulate the expression of TNFα in HCC cells. More importantly, we found the expression level of PIM2 increased with the progression of liver cirrhosis, and PIM kinase inhibitor AZD1208 treatment could effectively attenuate HCC cells’ tumorigenic ability both in vitro and in vivo. Collectively, our study revealed the interaction between an inflammatory factor and a proto-oncogene that contributed to tumorigenesis and progression of HCC, and PIM kinase inhibition may serve as a therapeutic target in the treatment of HCC.

炎症因子和致癌基因的激活均在人类肝细胞癌（HCC）的发生和发展中起着关键作用。但是，这两者之间的相互作用还没有得到很好的研究。在这项研究中，我们发现受TNFα，Pim-2原癌基因，丝氨酸/苏氨酸激酶（PIM2）的调节在肝癌中高表达，并且与不良预后（P  = 0.007）和肿瘤复发相关（P = 0.014）。功能研究表明，PIM2可以增强细胞增殖，细胞运动，血管生成，化学耐药性以及体内致瘤性和HCC转移的能力。机理研究表明，PIM2可以通过上调RIPK2的磷酸化水平来激活NF-κB信号通路。有趣的是，TNFα处理可以诱导PIM2的表达，而PIM2的过表达又可以上调HCC细胞中TNFα的表达。更重要的是，我们发现PIM2的表达水平随着肝硬化的发展而增加，PIM激酶抑制剂AZD1208的治疗可以有效地减弱HCC细胞的体内外致癌能力。总的来说，