短肽研究领域的新进展揭示细胞内源性短肽是具有生物学功能的新型分子，但国际上短肽的功能研究刚刚起步，短肽在肿瘤中的作用及机制更是鲜有见报道。HASEP是我们新鉴定的由长非编码RNA编码的短肽，它在人、鼠等多个物种中高度保守，但其功能和作用机制尚未见报道。我们前期研究发现，HASEP在肝癌中表达显著上调，沉默其表达导致细胞G1期阻滞、抑制细胞生长、并促进化疗药物诱导的细胞凋亡。以此为基础，本项目拟通过体内、外模型并结合临床标本研究HASEP对肝癌细胞增殖和凋亡等表型的调控作用，以及对肝癌发生发展的影响，鉴定与短肽相互作用的分子及其信号网络，并研究HASEP在肝癌中表达失调的分子机制。所得结果将阐明HASEP短肽的生物学功能和调控网络，并揭示肝癌发病的新机制，为肝癌防治提供新的靶标，因此具有重要的科学价值和临床意义。

Progress in the research field of small peptide (SEPs) reveals that cellular SEPs are new molecules with biological functions, yet our understanding about the biological function and its underlying mechanism of SEPs is still very limited. The effect of SEPs on the tumorigenesis has not been reported. Recently, we discovered that a transcripts that was previously annotated as an lncRNA gene, encodes a conserved small peptide (named HASEP). The small peptide HASEP was over-expressed in hepatocellular carcinomas (HCC), yet the biological function and its underlying mechanism of HASEP remains unknown. Our primary studies showed that silencing HASEP promoted G1 phase arrest of cell cycles and inhibited Hepatoma cell growth, and enhanced chemotherapeutic drug–induced cell apoptosis. Based on these findings, we will further investigate: 1) the role of HASEP on the proliferation and apoptosis of HCC cells and on the in vivo growth of HCCs; 2) the underlying regulatory mechanisms of HASEP in HCC development; 3) the mechanisms responsible for the deregulation of HASEP in HCCs. The results obtained will not only reveal the biological function and regulatory networks of SEPs, but also provide new targets for the prevention and antitumor therapy of HCCs.