我国是肝癌高发国家，全球新发肝癌一半以上在中国，较低的肝癌早期诊断率导致我国肝癌死亡率居高不下。诊断率低的主要原因是缺少有效的肿瘤标志物，研究证明经过有效救治的早期肝癌，5年存活率能超过50%，因而研究新的肝癌肿瘤标志物意义重大。环状RNA作为近年来的研究热点，与肿瘤的发生发展关系密切。我们前期发现环状RNA circ-PRKAA1在肝癌病人血浆中显著上调。敲低circ-PRKAA1，肝癌细胞中的中性脂肪酸累积明显减少，参与脂肪酸从头合成的关键蛋白ACLY、SREBF1前体和成熟体都明显下调。据此提出假说：“circ-PRKAA1通过促进脂肪酸从头合成调控肝癌细胞的脂代谢重编程，进而促进肝癌的发生发展”。本项目拟从分子与细胞、动物以及临床三个水平阐明circ-PRKAA1影响肝癌发生发展的机理，它的实施将为确定circ-PRKAA1作为肝癌早期诊断标志物以及肝癌治疗的分子靶标提供理论依据。

China is a country with high incidence of liver cancer. More than half of the new liver cancers in the world are in China. The low early diagnosis rate of liver cancer leads to high mortality rate of liver cancer in China. The main reason for the low early diagnosis rate of liver cancer is the lack of effective tumor markers. It has been proved that the 5-year survival rate of early diagnosed liver cancer can exceed 50% after effective treatment, so it is of great significance to study new tumor markers of liver cancer. As a new research hotspot in recent years, circular RNA is closely related to the occurrence and development of tumor. Our previous study found that circular RNA circ-PRKAA1 was significantly upregulated in the blood of patients with liver cancer. In addition, the key proteins involved in the de novo synthesis of fatty acids, such as ACLY, SREBF1 precursor and mature forms, were significantly decreased. Therefore, we propose the hypothesis that "circ-PRKAA1 enhances the occurrence and development of liver cancer by promoting the de novo synthesis of fatty acids to regulate the lipid metabolism reprogramming of liver cancer cells". The purpose of this project is to elucidate the specific mechanism of circ-PRKAA1 affecting the occurrence and development of liver cancer at the molecular and cellular, animal and clinical levels. The specific implementation of this project will provide theoretical basis for the final determination of circ-PRKAA1 as a new early diagnosis marker of liver cancer and a molecular target for liver cancer treatment.