Abstract:

Objective

To investigate the role of pseudouridine synthase 7 （PUS7） and its molecular mechanism in colon cancer clinical specimens and cells.

Methods

Data profiles including colon cancer tissue samples and normal tissue samples were downloaded from the Cancer Genome Atlas database.Subsequently， 200 differentially expressed genes were investigated by protein-protein interaction （PPI）network.RT-PCR and Western blotting were used to detect the gene expression level.CCK-8 assay， colony formation assay， Transwell assay and flow cytometry were used to detect cell activity， proliferation， invasion and apoptosis， respectively.

Results

PUS7 was a key gene in the most important module of the PPI network.The expression of PUS7 was upregulated in colon cancer tissues and cell lines.In 60 colon cancer patients， overexpression of PUS7 was significantly associated with low survival （P＜0.05）.Inhibition of PUS7 significantly reduced cell proliferation and invasive capacity， while overexpression of PUS7 promoted cell proliferation and invasive capacity （P＜0.05）.In PUS7-disrupted or overexpressed colon cancer cells， the protein levels of activated cysteine-containing aspartate protein hydrolase 3/9 （cleaved caspase-3/9）， c-myc，E-cadherin， and Vimentin were significantly regulated （P＜0.01）.Overexpression of PUS7 significantly upregulated the phosphorylation levels of PI3K， AKT and mTOR （P＜0.01）.

Conclusion

Overexpression of PUS7 can upregulate the proliferation and invasion ability of colon cancer cells and inhibit apoptosis by activating the PI3K/AKT/mTOR signaling pathway.

Key words: PUS7, Colonic neoplasms, Cell proliferation, Neoplasm invasiveness, PI3K/AKT/mTOR signaling pathway, Computational biology