癌基因的异常激活是导致肝癌发生与发展的重要原因之一。探索并研究肝癌中新基因的异常表达及其生物学功能，对揭示肝癌的发病机制，开发新的治疗药物以及预后判断都具有重要的指导意义。课题组前期研究显示SMPDL3A是一个可以促进肝癌细胞增殖、抑制凋亡的新癌基因，并且干扰SMPDL3A表达可以促进肝癌细胞中鞘磷脂（SM）的生成。其机制可能是SMPDL3A表达受转录因子HIC1的调控，并与鞘磷脂合酶（SGMS）相互作用导致肝癌细胞中SM生成减少，从而促进了肝癌的发生发展。项目组拟通过分子、细胞、动物模型和临床样本等多角度，探讨HIC1对SMPDL3A的转录调控，SMPDL3A在肝癌中的生物学功能，以及SMPDL3A与SGMS的相互作用影响SM生成的分子机制。本研究旨在阐明SMPDL3A基因的转录激活，及其在肝癌中的生物学功能和具体作用机制，为肝癌的临床诊治及预后判断提供新思路。

Abnormal activation of oncogenes is one of the major causes of the occurrence and development of hepatocellular carcinoma (HCC). It is significant to explore and study the abnormal expression of novel genes and their biological functions in revealing the pathogenesis of HCC, developing new therapeutic drugs and judging prognosis. Our previous study showed that SMPDL3A is a novel oncogene that can promote proliferation of HCC cell and inhibit its apoptosis. Besides，interference of SMPDL3A expression can promote the production of sphingomyelin (SM) in HCC cells. The possible mechanism is that SMPDL3A expression is regulated by transcription factor HIC1 and interacts with sphingomyelin synthase (SGMS) leading to the decrease of SM, which results in the occurrence and development of HCC. We intend to investigate the transcriptional regulation of SMPDL3A by HIC1, the biological function of SMPDL3A in HCC, and the interaction between SMPDL3A and SGMS which influences SM production through molecular, cellular, animal models and clinical samples. This study aims to elucidate the transcriptional activation of SMPDL3A, biological function of SMPDL3A and its specific molecular mechanism that will provide a new idea for the clinical diagnosis, treatment and prognosis in HCC.