长非编码RNA编码的微肽在p53信号通路中的功能和机制研究

长非编码RNA（lncRNA）编码的微肽（micropeptide）是一类新的调控分子，参与各种生物体生理和病理过程的调控。然而，这些微肽在细胞重要信号通路（如p53通路等）中的表达调控及功能机制尚不清楚。我们前期在激活p53的肝癌细胞模型中进行的转录组和翻译组分析发现，p53转录调控了一批新的由长非编码RNA编码的微肽。由此我们推测，长非编码RNA编码的微肽是p53信号通路的重要新成员，并协同p53在细胞生命活动中发挥重要的调控作用。在此基础上，本项目拟结合实验方法和RNA-seq、Ribo-seq和ChIP-seq等高通量测序手段，系统鉴定肝癌中p53调控的长非编码RNA及其编码的微肽，阐明这些微肽表达调控的分子机制，解析p53调控的微肽在DNA损伤修复、肿瘤发生发展等生物学过程中的作用，揭示微肽与p53信号通路之间的协同调控机制，为肿瘤等疾病研究提供新的潜在靶标。

Long non-coding RNAs (lncRNAs) encoded micropeptides are a new class of regulatory molecules and involve in the regulation of diverse physiological and pathological processes. However, the expression and functional importance of these micropeptides in cellular signaling pathway remain to be elucidated, including the p53 pathway. In our previous studies, the transcriptome and translatome analyses in hepatoma carcinoma cells upon p53 activation showed that a batch of new lncRNAs encoded micropeptides were transcriptionally regulated by p53. Therefore, we hypothesize that these micropeptides are important new members of the p53 signaling pathway and play critical roles in regulating various cellular biological processes by synergizing with p53. We thus set out to systematically explore micropeptides encoded by p53-regulated lncRNAs in p53 signaling pathway based on integrative approach of experiments and next-generation sequencing, including RNA-seq, Ribo-seq and ChIP-seq. Moreover, we will investigate the expression and transcriptional regulation of micropeptides that are directly controlled by p53, as well as the function of those p53-regulated micropeptides involved in DNA damage repair, tumorigenesis and progression. Altogether, the study will expand our understanding on the mechanism of coordinated regulation between micropeptides and the p53 signaling pathway, and provide new potential targets for tumors and other diseases.