PAIP1 promote the progress of liver cancer via regulating expression of immune and inflammatory response associated genes. PAIP1 promote the progress of liver cancer via regulating expression of immune and inflammatory response associated genes

Poly(A) binding protein interacting protein 1 (PAIP1) is a translation regulator and also regulate the decay of mRNA. PAIP1 has also been reported to be a marker of increased invasive potential of liver cancer. However, the underlying molecular mechanism of PAIP1 in liver cancer is still unclear. Here, the gene expression profile of HepG2 cells transfected with PAIP1 shRNA (shPAIP1) was compared with cells transfected with empty vector (shCtrl). The results showed that shPAIP1 extensively affects the transcriptional level of 893 genes in HepG2 cells. In particular, GO analysis showed that a large number of up-regulated genes were annotated with terms including cell cycle and WNT receptor signaling pathway. The down-regulated genes were enriched in some pathways including immune response and inflammatory response. qPCR confirmed that PAIP1 knockdown significantly negatively or positively affected the expression of selected DEGs including interleukin-10 signaling pathway genes in HepG2 cells. Expression analysis of TCGA revealed that PAIP1 had positive correlations with IL1R2 and PTAFR in liver tumor tissue, respectively. Our results demonstrated that PAIP1 was not only a translation regulator, but also a transcription regulator in liver cancer. Thus, our study provides important cues for further study on the regulatory mechanism of PAIP1 in liver cancer Overall design: Transcrptional profile of HepG2 cells with/without PAIP1 Knockdown were generated

Poly(A)结合蛋白互作蛋白1（Poly(A) binding protein interacting protein 1，PAIP1）是一类翻译调控因子，同时可调控mRNA的降解过程。已有研究报道PAIP1可作为肝癌侵袭潜能升高的标志物，但目前PAIP1在肝癌中发挥作用的潜在分子机制仍不明确。本研究将转染PAIP1短发夹RNA（short hairpin RNA, shRNA）的HepG2细胞（shPAIP1组）与转染空载体的对照组细胞（shCtrl组）的基因表达谱进行对比分析。结果显示，shPAIP1可广泛影响HepG2细胞中893个基因的转录水平。具体而言，基因本体（Gene Ontology, GO）富集分析表明，大量上调基因富集于细胞周期、WNT受体信号通路等功能条目；下调基因则富集于免疫应答、炎症应答等通路。实时荧光定量PCR（quantitative real-time polymerase chain reaction, qPCR）验证结果显示，敲低PAIP1可显著正向或负向调控所选差异表达基因（differentially expressed genes, DEGs）的表达，包括白细胞介素-10信号通路相关基因。基于癌症基因组图谱（The Cancer Genome Atlas, TCGA）的表达分析显示，PAIP1在肝癌组织中分别与IL1R2及PTAFR呈正相关。本研究证实，PAIP1不仅是翻译调控因子，同时也是肝癌中的转录调控因子。综上，本研究为进一步探究PAIP1在肝癌中的调控机制提供了重要线索。整体实验设计：本研究构建了敲低PAIP1与未敲低PAIP1的HepG2细胞转录组表达谱。