肝纤维化是肝炎发展为肝硬化、肝癌的中间环节，有效的抗肝纤维化治疗对于肝癌的防治具有重要意义。抗肝纤维化首选中成药复方鳖甲软肝片在抗炎、抗纤维化及增强机体免疫功能等方面具有明显优势。然而，该方对于肝癌的干预特点和作用原理尚不清楚。本项目拟在前期工作基础上，基于肝纤维化和合并肝纤维化肝癌的临床样本，整合mRNA/miRNA/lncRNA多分子层面芯片和网络分析，系统鉴定肝纤维化-肝癌轴相关RNAs及竞争性内源RNA（ceRNA）组合；再利用本课题组已建立的中药靶标预测系统，获得复方鳖甲软肝片的候选靶标谱，并通过疾病相关RNAs/ceRNAs及药物靶标互作网络分析和实验验证，探索该方对肝纤维化-肝癌轴相关ceRNA调控网络的干预机制，明确其对合并肝纤维化肝癌的治疗作用。本项目将揭示复方鳖甲软肝片防治肝癌的潜能，有利于拓宽该方的应用范围及研究思路，也为肝癌的综合治疗提供新的理论基础和干预手段。

Hepatic fibrosis may lead to cirrhosis, which may progress to liver cancer, with an associated risk of liver failure and death. Effective anti-fibrosis treatment is of great significance for the prevention of liver cancer. Emerging clinical evidence suggests that traditional Chinese medicine (TCM) formula Fufang Biejia Ruangan Pills (FBRP) may be an efficient agent to attenuate the severity of liver inflammation and hepatic fibrosis, and improve the immune state of the whole body. However, its potential clinical applications and underlying mechanisms acting on hepatocellular carcinoma (HCC) with a hepatic fibrosis background remain unclear. To fill this gap, microarray detection of mRNAs, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) will be performed in this project using human hepatic fibrosis and HCC tissues. Following the bioinformatic analyses on RNA expression profiles and the construction of lncRNA-miRNA-mRNA network, the candidate mRNAs/miRNAs/lncRNAs/competing endogenous RNAs (ceRNAs) associated with hepatic fibrosis-HCC axis will be identified at a system level. Then, the putative targets for composite compounds contained in FBRP will be predicted using a TCM target prediction system which was established by our previous studies. After that, the drug target--disease-related RNA interaction network will be constructed and a list of major FBRP targets acting on HCC will be generated based on their topological features and their links to the candidate mRNAs/miRNAs/lncRNAs/ceRNAs associated with hepatic fibrosis-HCC axis. Further experimental validations in vivo and in vitro systems will be performed to verify our prediction results. This study will not only enrich the understanding of the process from hepatic fibrosis to HCC, but also offer a powerful evidence for the potential clinical applications of FBRP. It is helpful to broaden the scope of FBRP's clinical applications, as well as provide novel theoretical basis and therapeutic strategies for the comprehensive prevention and treatment of human HCC.