COMP Upregulates PI3K/AKT Signaling Pathway To Promote Proliferation And Migration Of Pancreatic Cancer Cells

Background:Pancreatic cancer(PC)is the most lethal type of malignancy,characterized by high invasiveness and no serious symptoms.Due to the low diagnostic accuracy of existing conventional methods such as abdominal ultrasound,CT,MRI,and endoscopic ultrasound(EUS),it is difficult to detect PC at an early stage.therefore,it is necessary to develop new diagnostic techniques to achieve early and accurate diagnosis.COMP is a cartilage oligomeric matrix protein that is commonly used as a potential biomarker of joint destruction in osteoarthritis.Studies conducted recently have revealed a correlation between COMP and the emergence of tumors such as breast,prostate,liver,and early colon cancer,but the biological behavior of COMP on PC is currently unknown.The aim of this paper is to investigate the effect of COMP on PC cell phenotype,as well as to further explore its mechanism.Methods:With the help of bioinformatics,the GEPIA database was used to analyze the expression of COMP in different tumors and in PC,and to analyze whether COMP correlated with the overall survival and disease-free survival of PC patients.The expression of COMP in PC was similarly analyzed using the GEO database,and GO,KEGG enrichment analysis was used to understand the function of COMP and the pathway of enrichment.In the experiments,COMP expression was determined in PC cell lines and PC tissue samples using qRT-PCR.Through various experiments such as cell counting kit-8(CCK-8),plate cloning and 5’-Ethynyl-2’-deoxyuridine(EdU),we investigated the cellular enrichment and explored the cell migration in depth by Transwell assay and scratch assay.Finally,the related pathway proteins were further validated by Western blot assay.Results: Bioinformatic analysis showed that COMP expression was significantly elevated in some cancer types.qRT-PCR results showed that COMP was highly expressed in PC tissues compared to non-pancreatic tissues,also in PC cells.COMP overexpression was associated with poor prognosis in PC.SiRNA-silenced COMP inhibited PC cells’ proliferation and migration capabilities,and KEGG enrichment analysis revealed a strong connection between COMP and the PI3K/AKT signaling pathway.Western blotting further confirmed that si RNA-silenced COMP significantly decreased the protein expression of both p-PI3K and p-Akt.Conclusion: The current study found that PC patients have a higher level of COMP,which is linked to a worse prognosis.Furthermore,COMP silencing contributes to a better understanding of the etiology of PC by inhibiting the PI3K/Akt pathway,which in turn reduces PC cell proliferation and migration.