肝细胞癌（HCC）发病分子机制复杂，是限制其诊治水平提高的关键问题，而线粒体功能异常与HCC的发生发展密切相关，但其具体调控机制尚不明确。我们首次发现长链非编码RNA MALAT1在HCC线粒体中高度富集，并与线粒体基因组上调控线粒体DNA复制、转录的功能区域及部分编码氧化呼吸链复合物亚基的基因区域结合。提出细胞核内DNA转录的MALAT1穿梭转运至线粒体，调控线粒体氧化磷酸化代谢等过程，影响HCC发生发展的全新分子机制。本项目在应用靶向线粒体的LwaCas13a RNA编辑技术的基础上，综合应用线粒体RNA荧光原位杂交、RNA逆转录相关捕获法等关键技术，对MALAT1在HCC线粒体中富集的临床意义、穿梭转运的分子机制、恶性生物学功能的影响和在线粒体功能调控中的分子机理等方面进行探究，揭示HCC发生发展的新机制，从而为HCC分子标志物和治疗靶点的发掘奠定基础。

The molecular mechanism of hepatocellular carcinoma (HCC) is complex, which is the key problem to limit the improvement on diagnosis and treatment of HCC. However, the mitochondrial dysfunction is closely related to the occurrence and development of HCC, but the specific regulatory mechanism is remain unclear. We firstly discover that long non-coding RNA MALAT1 is highly enriched in mitochondria of HCC cells and binds to the functional regions of the mitochondrial genome that regulate mitochondrial DNA replication, transcription, and the regions of genes that partially encode the subunits of the oxidative respiratory chain complex. Thus, we propose that MALAT1, transcribed by the intranuclear DNA, transports to mitochondria and regulates mitochondrial oxidative phosphorylation metabolism and other processes to influence the occurrence and development of HCC. This study is based on the application of RNA editing with LwaCas13a targeting the mitochondria. Mitochondrial RNA fluorescence in situ hybridization, RNA reverse transcription associated trap assay and other key technologies will be applied in this study, in order to investigate the clinical significance, the molecular mechanism of transportation of MALAT1 into the mitochondria, the influence of biological function and its molecular mechanism associated with the enrichment of MALAT1 in the mitochondria. It is aimed to reveal the novel mechanism of HCC occurrence and development, so as to make the foundation for the exploration the potential for MALAT1 in mitochondria of HCC as the molecular marker and therapeutic target.