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PAIP1 在转录水平上调节肝癌细胞中免疫和炎症反应相关基因的表达。

PAIP1 regulates expression of immune and inflammatory response associated genes at transcript level in liver cancer cell.

机构信息

Department of Laboratory Medicine, Baoan Central Hospital of Shenzhen, The Fifth Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.

Department of Infectious Medicine, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, China.

出版信息

PeerJ. 2023 Apr 21;11:e15070. doi: 10.7717/peerj.15070. eCollection 2023.

Abstract

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 roles and underlying molecular mechanism of PAIP1 in liver cancer is still unclear. Here, cell viability and the gene expression profile of liver cancer line HepG2 transfected with PAIP1 siRNA was compared with cells transfected with non-targeting control siRNA. The results showed that PAIP1 knockdown inhibited cell viability, and extensively affects expression of 893 genes at transcriptional level in HepG2 cells. Gene function analysis showed that a large number of PAIP1 up-regulated genes were enriched in term of DNA-dependent transcription and the down-regulated genes were enriched in some pathways including immune response and inflammatory response. qPCR confirmed that PAIP1 knockdown positively regulated the expression of selected immune and inflammatory factor genes in HepG2 cells. Expression analysis of TCGA revealed that PAIP1 had positive correlations with two immune associated genes IL1R2 and PTAFR in liver tumor tissue. Taken together, our results demonstrated that PAIP1 was not only a translation regulator, but also a transcription regulator in liver cancer. Moreover, PAIP1 could function as a regulatory factor of immune and inflammatory genes in liver cancer. Thus, our study provides important cues for further study on the regulatory mechanism of PAIP1 in liver cancer.

摘要

多聚(A)结合蛋白相互作用蛋白 1(PAIP1)是一种翻译调节因子,也可以调节 mRNA 的降解。PAIP1 也被报道为肝癌侵袭潜能增加的标志物。然而,PAIP1 在肝癌中的作用和潜在的分子机制尚不清楚。在这里,我们比较了转染 PAIP1 siRNA 的肝癌细胞系 HepG2 与转染非靶向对照 siRNA 的细胞的细胞活力和基因表达谱。结果表明,PAIP1 敲低抑制细胞活力,并在 HepG2 细胞中转录水平广泛影响 893 个基因的表达。基因功能分析表明,大量上调的 PAIP1 基因富集于 DNA 依赖性转录,而下调的基因富集于一些通路,包括免疫反应和炎症反应。qPCR 证实,PAIP1 敲低可正向调节 HepG2 细胞中选定的免疫和炎症因子基因的表达。TCGA 的表达分析表明,PAIP1 在肝肿瘤组织中与两个免疫相关基因 IL1R2 和 PTAFR 呈正相关。总之,我们的研究结果表明,PAIP1 不仅是一种翻译调节因子,也是肝癌中的一种转录调节因子。此外,PAIP1 可作为肝癌中免疫和炎症基因的调节因子。因此,我们的研究为进一步研究 PAIP1 在肝癌中的调控机制提供了重要线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/259c/10124545/a2fe6241dd70/peerj-11-15070-g001.jpg

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