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

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 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE185866 | GEO | 2023/03/12

REPOSITORIES: GEO

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Project description:The proinflammatory cytokine, TNFalpha is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Considering this, gene transcription profiling was examined in control and TNFalpha treated HepG2 cells. Results indicated that TNFalpha could significantly alter the expression of a significant number of genes; most of them were functionally distributed among molecular functions like catalytic activity, binding, molecular transducer activity, transporter activity, translation and transcription regulator activities or enzyme regulator activity. Also, within genes up-regulated by TNFalpha, several GO terms related to lipid and fat metabolism were significantly overrepresented indicating global dysregulation of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in immunoglobulin receptor activity and IgE binding thereby indicating a compromise in immune defense mechanism(s) apart from those involved the DNA binding and protein binding categories. The interacting network of “lipid metabolism, small molecule biochemistry” was derived to be significantly affected that correlated well with the top canonical pathway of “biosynthesis of steroids” and molecular and cellular function of “lipid metabolism”. All these indicate TNFalpha to be significantly altering the transcriptome profiling within HepG2 cells with genes involved in lipid and steroid metabolism being the most favoured. This study suitably addresses the genes that determine TNFalpha mediated alterations within the hepatocyte mainly the phenotypes of hepatic steatosis and fatty liver that are associated with several hepatic pathological states. HepG2 cells were maintained in DMEM supplemented with 10% fetal calf serum with 1% antibiotic-antimycotic. On attaining confluency, cells were serum starved overnight and incubated in the absence (control) and presence of TNFalpha (0.5nM, 12h). On termination of incubation, total RNA was isolated, reverse transcribed to cDNA and subjected to in vitro transcription to produce biotinylated cRNA that was hybridized to the human array chip (Human Genome U133 Plus 2.0, Affymetrix) according to the manufacturer's instructions. Images were scanned using the GeneChip 3000 7G scanner (Affymetrix) and analysed. The experiment was performed with triplicates of each set (Control and TNF alpha treated). This experiment was reloaded in November 2010 after additional curation.

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

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