摘要
免疫应答在调控肝癌等肿瘤发生中发挥双刃剑作用,只有慢性非可控炎症才引发肝细胞癌(HCC),这得到了大量动物模型和临床数据的支持.在慢性肝炎中浸润的免疫细胞直接杀伤肝细胞、炎症因子引发的细胞凋亡和坏死诱发肝细胞持续性炎症坏死与再生,这直接增加肝细胞突变的风险.NF-κB、JAK-STAT、MAPK/ERK等通路以及miR-122、miR-124、miR-637、miR-520e、miR-195等小RNA均参与慢性炎症-HCC的转化.阻断引发非可控炎症的诱因、直接靶向炎症因子以及干预慢性炎症引发HCC的关键信号通路,对于研发新型HCC的网络治疗方案至关重要.
This review provides an insight into chronic infection and inflammation-associated hepatocellular carcinoma and potential therapeutic strategies. The inflammatory immune response plays a dual role in cancer development, including hepatocellular carcinoma （HCC）. Only chronic and unresolved inflammation induces HCC, which is supported by enormous studies on animal models and clinical analyses. In chronic hepatitis, direct killing of hepatocytes by liver infiltrated lymphocytes and inflammatory cytokines-induced hepatocyte apoptosis and necrosis induce persistent rico-inflammation and hepatocyte generation, which increases the risk of genetic mutation and neoplastic transformation of hepatocytes. Several inflammation-related signaling pathways are involved in hepatocarcinogenesis, including NF-KB, JAK-STAT and MAPK/ERK signaling. In addition, microRNAs （e.g. miR-122, miR124, miR-637, miR-520, and miR-195） also play a key role in HCC development. Therefore, it will be attractive to design therapeutic strategies against HCC by blocking inflammation-inducing factors, targeting pro-inflammatory cytokines and chemokines, and intervening key pathways that orchestrate neo-inflammation networks in HCC development.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2014年第1期17-23,共7页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目(31230026
91029724
81021003
81102018)~~
关键词
慢性炎症
肝细胞癌
小RNA
信号通路
治疗策略
chronic inflammation, HCC, microRNAs, signaling pathway, therapeutic strategy
