| Background:Pancreatic cancer is one of the most highly malignant tumors in the digestive system.Its onset is occult and develops rapidly.The typical feature is poor prognosis.Radical surgical resection is currently the only definitive and effective treatment.However,only 15%-20% of patients can undergo surgical treatment due to the complex and ever-changing mechanism of pancreatic cancer.Given the lack of effective comprehensive treatment options,researchers are required to explore the underlying mechanisms of the onset of pancreatic cancer and find new treatment options.CKS2 is a member of the family of cyclin-dependent kinase regulatory subunits.Previous studies have shown that CKS2 is abnormally expressed in a variety of tumors and is associated with the prognosis of tumors,but it has not been reported in pancreatic cancer.Our high-throughput sequencing of pancreatic cancer tissues in the earlier period of this study found that CKS2 is highly expressed in pancreatic cancer tissues.In addition,the GO analysis of CKS2 and its co-expressed gene showed that its function was mainly related to nuclear division,cell proliferation and cell cycle.Objective:1)Explore the expression of CKS2 in pancreatic cancer and its clinical significance.2)Explore the effects of CKS2 on the function of pancreatic cancer cells and the underlying molecular mechanisms.Method:1)The TCGA and GTEx databases were used to analyze the correlation between CKS2 m RNA expression and proliferation marker MKI67 in pancreatic cancer samples,and the correlation between CKS2 m RNA expression and disease prognosis.The expression of CKS2 protein in the pancreatic cancer specimens of this center was detected by immunohistochemistry.The correlation between the expression of CKS2 protein and clinicopathological features and prognosis was analyzed by statistical methods.2)The expression level of CKS2 in pancreatic cancer cell lines was detected by fluorescence quantitative PCR and Western Blot.Lentiviral silencing and overexpression of CKS2 were used to construct corresponding stable cell lines.The effect of CKS2 on the proliferation of pancreatic cancer cells was examined by CCK-8,EDU,plate cloning,and subcutaneous tumorigenesis in nude mice.The effect of CKS2 on invasion and migration of pancreatic cancer cells was examined by Transwell assay.3)The mechanism of CKS2 promoting pancreatic cancer cell proliferation was explored by flow cytometry and Western Blot assay.Results:1)TCGA and GTEx databases showed that CKS2 m RNA was highly expressed in pancreatic cancer tissues,CKS2 m RNA was positively correlated with Mki67 expression,and pancreatic cancer patients with high expression of CKS2 m RNA had significantly shorter overall survival and disease-free survival.2)CKS2 protein was highly expressed in pancreatic cancer tissues and its expression level was significantly correlated with T stage,tumor size,tissue differentiation,and survival time.High expression of CKS2 was associated with poor prognosis of pancreatic cancer patients and may be an independent risk of prognosis factor.3)Silencing CKS2 can inhibit pancreatic cancer cell proliferation,invasion,and migration.Overexpression of CKS2 showed the opposite trend.4)CKS2 affected cell proliferation by regulating the apoptosis and cycle of pancreatic cancer cell lines.Silent CKS2 group had more apoptosis and delayed G2/M phase than the control group.Overexpression of CKS2 showed the opposite trend.5)CKS2 can regulate the expression of Bcl-2,Bax,Caspase3,Cdc25 C,GADD45a,P21 and P53.Conclusion:1)The transcript level and protein level of CKS2 were significantly higher in pancreatic cancer tissues than in adjacent tissues and were closely related to the occurrence and development of pancreatic cancer and poor prognosis.2)CKS2 can regulate the proliferation,invasion,and migration of pancreatic cancer cell lines.3)CKS2 may promote pancreatic cancer cell proliferation by affecting the P53 pathway. |
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