HRSPM1短肽的功能网络及其在肝癌生长转移中的作用

短肽是指由短的开放阅读框(short open reading frame, sORF)翻译生成的长度小于100个氨基酸的多肽。国际上短肽的功能研究刚刚起步，短肽在细胞生命活动及人类疾病中的作用鲜有报道。我们前期发现了一个含有56个氨基酸、在物种间高度保守、定位于线粒体、在肝癌（HCC）中表达下调、且能抑制肝癌细胞运动迁移的短肽，将其命名为HRSPM1（HCC-Related Short Peptide in Mitochondria），并制备了HRSPM1的抗体及基因敲除鼠。以此为基础，本项目拟结合体内外模型，鉴定HRSPM1对细胞生命活动及肝癌生长转移的调控作用；阐述HRSPM1发挥作用的分子机制；揭示调控HRSPM1表达的机制及其在肝癌细胞中失调的原因。研究结果有助于阐明新型短肽的生物学功能及调控网络，揭示肝癌发病的新机制，为肝癌防治提供新的靶分子，因此具有重要的科学价值和临床意义。

Short peptides refer to the polypeptides of less than 100 amino acids, which are encoded by the short open reading frames (sORFs). The function of short peptide and its implication in disease remain largely unknown. We have identified a short peptide that contains 56 amino acids and is located in mitochondria and conserved across different species. It is downregulated in hepatocellular carcinoma (HCC) and may inhibit the migration of HCC cells. We therefore name it HRSPM1 (HCC-Related Short Peptide in Mitochondria). We have also developed the antibody against HRSPM1 and the HRSPM1-knockout mice. Based on these preliminary studies, we will further investigate: 1) the regulatory role of HRSPM1 in cell activities and in the growth and metastasis of HCC; 2) how HRSPM1 exerts its function; 3) the mechanisms that regulate HRSPM1 expression and that cause HRSPM1 downregulation in HCC. The results obtained will reveal the biological function and regulatory networks of a novel short peptide, disclose the new mechanism of HCC development, and provide new targets for the prevention and therapy of HCC.