选择性多聚腺苷酸化(APA)是基因表达的一种重要转录后调控方式，参与细胞分化、免疫激活和肿瘤形成等生物学过程。最近研究发现剪切因子元件NUDT21影响恶性胶质瘤细胞APA模式并发挥肿瘤抑制功能。而NUDT21对其他肿瘤APA的影响及其功能仍有待阐明。我们前期工作发现肝癌组织和肝癌细胞系中NUDT21表达明显下调，抑制NUDT21的表达增强肝癌细胞的增殖、迁移和克隆形成能力，提示NUDT21 在肝癌细胞中发挥肿瘤抑制作用。本项目拟通过我们研发的3T-seq技术，在含有不同NUDT21表达水平的肝癌细胞中开展全基因组范围的APA位点研究，明确NUDT21对肝癌细胞APA的影响，并阐明NUDT21如何通过改变相关基因poly(A)选择性使用和3’UTR而发挥其肿瘤抑制的功能。这一工作不仅可以推进APA和肿瘤关系的理解，而且将对于探索NUDT21在不同肿瘤中所发挥的作用提供借鉴。

Alternative polyadenylation (APA) is an important post-transcriptional regulation for gene expression. APA is implicated in cellular differentiation, immune activation and tumor formation. A recent report revealed cleavage factor component NUDT21 modulates APA pattern in glioblastoma cells and suppresses glioblastoma tumorigenicity. However, it remains to be elucidated that whether NUDT21 has an effect on APA pattern in other types of cancer cells. In our pilot work we observed NUDT21 is down-regulated in both liver cancer tissue and hepatocellular carcinoma (HCC) cells. Suppression of NUDT21 promotes proliferation, migration and clone formation of HCC cells, suggesting it functions as a tumor suppressor. With 3T-seq developed by ourselves, in this project we will perform a genome-wide APA profiling analysis in HCC cells with various expression levels of NUDT21. We will investigate the effect of NUDT21 on APA selection and how it exert the tumor suppressor function on HCC cells by modulating APA usage and 3’UTR. This work will improve the understanding of relation between APA and tumor, and provide some insights for characterizing NUDT21 function in other types of cancer.