Zhou Y, Wu P-W, Yuan X-W, Li J, Shi X-L
Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Eur Rev Med Pharmacol Sci. 2016;20(2):250-63.
Hepatocellular carcinoma (HCC) is characterized by progressive development and poor prognosis against a background of chronic inflammation. Interleukin (IL)-17A is an important proinflammatory cytokine that contributes to inflammatory pathology and tumor microenvironment. Research on autophagy has increasingly focused on its role in inflammation. Thus, we investigated the effect of IL-17A on the progression of HCC through the autophagic pathway.
The expression and prognostic values of IL-17A and autophagic gene Beclin-1 were determined using immunohistochemistry in 83 HCC patients after resection. The effects and underlying molecular mechanisms of IL-17A on human HCC were explored in vitro using recombinant human IL-17A.
High expression of IL-17A and low expression of Beclin-1 were associated with worse TNM stage in HCC patients. And the level of autophagy was lower in tumor tissues compared with tumor-adjacent tissues. In vitro, recombinant human IL-17A inhibited starvation-induced autophagy and maintained cell viability through activating TAK1-binding protein 2 (TAB2 and TAK1-binding protein 3 (TAB3)-inducing p38 mitogen-activated protein kinase (MAPK) in Huh7 and HepG2 HCC cells. IL-17A promoted migration of HCC cells through the TAB2/p38 MAPK and TAB3/p38 MAPK pathways.
IL-17A promotes migration of HCC cells and prevents autophagic cell death from starvation by activating TAB2/p38 MAPK and TAB3/p38 MAPK.
肝细胞癌（HCC）的特征是在慢性炎症背景下进行性发展且预后不良。白细胞介素（IL）-17A是一种重要的促炎细胞因子，有助于炎症病理和肿瘤微环境。自噬研究越来越关注其在炎症中的作用。因此，我们通过自噬途径研究了IL-17A对HCC进展的影响。
采用免疫组织化学法检测83例HCC患者术后IL-17A和自噬基因Beclin-1的表达及预后价值。使用重组人IL-17A在体外探讨IL-17A对人HCC的影响及其潜在分子机制。
IL-17A高表达和Beclin-1低表达与HCC患者较差的TNM分期相关。与癌旁组织相比，肿瘤组织中的自噬水平较低。在体外，重组人IL-17A通过激活Huh7和HepG2 HCC细胞中的TAK1结合蛋白2（TAB2）和TAK1结合蛋白3（TAB3）诱导p38丝裂原活化蛋白激酶（MAPK）来抑制饥饿诱导的自噬并维持细胞活力。IL-17A通过TAB2/p38 MAPK和TAB3/p38 MAPK途径促进HCC细胞迁移。
IL-17A通过激活TAB2/p38 MAPK和TAB3/p38 MAPK促进HCC细胞迁移并防止饥饿诱导的自噬性细胞死亡。
