PCGF3 Promotes The Proliferation And Migration Of Non-small Cell Lung Cancer Cells Via PI3K/AKT Signaling Pathway

Objective:PCGF3 is a Polycomb Group Ring Finger(PCGF1-6)homolog and is one of the key components of the PRC1 complex.It has been shown that PCGF3 mutations are one of the key molecules in the alteration of intraductal papillary mucinous tumor subtypes,where PCGF3 is upregulated in pancreatic tumors and associated with signaling.Combining previous research reports and the current status of PCGF3 research in the field of oncology,the effect of PCGF3 on the biological function of non-small cell lung cancer(NSCLC)remains unclear;therefore,this study investigated the potential role of PCGF3 in NSCLC and the related molecular mechanisms.Methods: Bioinformatics analysis for PCGF3 to investigate its expression in lung cancer;86 lung cancer tissues were selected for immunohistochemical experiments to detect the protein expression and localization of PCGF3 in lung cancer tissues and to analyze the clinicopathological correlates;The effects of PCGF3 on the proliferation and migration of NSCLC cells were investigated in A549 and H1299 by up-and down-regulation of PCGF3 expression followed by MTT,colony formation assay and cell migration assay;The effect of PCGF3 on proliferation-related proteins,migration-related proteins and PI3K/AKT signaling pathway was also investigated by Western blot;after adding PI3K-specific inhibitor LY294002,relevant reversion experiments were performed.Results: 1.The UALCAN and GEPIA databases showed that the expression of PCGF3 was higher in lung cancer tissues than in normal lung tissues;The UALCAN database showed that the expression of PCGF3 in different stages of lung cancer was higher than that in normal lung tissue.Immunohistochemical results suggested that the expression of PCGF3 was higher in non-small cell lung cancer tissues than in normal tissues adjacent to cancer.Analysis of clinicopathological correlates showed that PCGF3 was positively correlated with lymph node metastasis and p-TNM stage,and Kaplan-Meier database showed that PCGF3 was associated with poor prognosis of lung cancer patients.2.Altered PCGF3 expression in A549 and H1299 cells,colony formation assay,MTT assay and Western blot showed that PCGF3 could increase the expression of proliferation-related proteins and promote the proliferative ability of NSCLC.3.Altered PCGF3 expression in A549 and H1299 cells,cell migration assays and Western blot results showed that PCGF3 was able to increase the expression of migration-associated proteins and promote the migratory ability of NSCLC.4.Western blot results showed that PCGF3 could positively regulate the PI3K/AKT signaling pathway.5.After the addition of PI3K/AKT signaling pathway inhibitor to inhibit this signaling pathway,combined with Western blot,MTT,colony formation assay and cell migration assay,it was determined that PCGF3 promotes the proliferation and migration of non-small cell lung cancer cells through PI3K/AKT signaling pathway.Conclusion:1.PCGF3 was overexpressed in non-small cell lung cancer tissues,and its protein expression level was positively correlated with lymph node metastasis and TNM stage of the tumor,and was associated with poor patient prognosis.2.PCGF3 promotes the proliferation of NSCLC by regulating the expression of Cyclin B1,Cyclin D1 and CDK4.3.PCGF3 promotes the migration of NSCLC by regulating the expression of Rho A,Rho C,CDC42.4.PCGF3 promotes proliferation and migration of NSCLC through positive regulation of the PI3K/AKT signaling pathway.