| Background:Endometrial cancer is a malignant tumor of the reproductive system.Studies found that endometrial cancer had a closed relationship with obesity,diabetes,and hypertension.Chemerin is highly expressed in adipose tissue and can participate in a variety of metabolic processes,regulate adipocyte differentiation and be associated with obesity.Chemerin binds its receptor CMKRL1 to increase the incidence of insulin resistance and inflammation-related cancers.Recent studies have shown that chemerin plays a role in a variety of insulin resistance-related diseases,such as obesity,hypertension,diabetes,and polycystic ovary syndrome.At present,there is no research on the correlation between chemerin and its receptor CMKLR1 with endometrial cancer.Objective: To investigate whether chemerin and its receptor CMKLR1 are associated with endometrial cancer,and the role of them in the development of endometrial cancer.Method : Collected inpatients with diagnosis as endometrial cancer(20 cases)in Tianjin Central Obstetrics and Gynecology Hospital as the endometrial cancer group,and selected the same period benign inpatients with matched by BMI served as the control group.The serum chemerin expression level was detected by ELISA method.The expression of CMKLR1 were detected by immunohistochemistry.Use TCGA database to explore the relationship between CMKLR1 and clinical pathological parameters with endometrial cancer.Human endometrial cancer cell lines were added with different concentrations of chemerin,and the effects on cell proliferation and migration ability were observed by CCK-8 and wound healing experiment.After lentivirus transfected endometrial cancer cell line HEC-1B experiment,puromycin screening was used to obtain a stable clone with knockdown CMKLR1.CCK-8 kit was used to detect the difference of proliferation ability between si CMKLR1 group and HEC-1B cell with vector;wound healing and Transwell chamber tests were used to detect the migration ability changing after knocking down CMKLR1 gene;Western Blot was used to detect CMKLR1 effect on Wnt signaling pathway.Result: The serum chemerin level of patients with endometrial cancer was 871.4±302.2 ng/ml,which was higher than that of the normal control group 727.8± 303.9ng/ml.But there was no significant difference in comparison(P=0.091).Immunohistochemistry showed that CMKLR1 expression was higher in endometrial cancer tissues than in adjacent tissues.Cytological results showed although added of recombined chemerin,there is no significant difference on the proliferation and migration of endometrial cancer cell lines compared with control group.Using CMKLR1-si RNA to establish stable clone cell line of HEC-1B.RT-PCR and Western Blot results showed that the m RNA and protein levels of the si CMKLR1 group were significantly lower than those of the control group(P<0.01);CCK-8experiment showed that compared with the control group,the cell proliferation ability of the si CMKLR1 group was decreased(P<0.01);wound healing and transwell chamber results showed that the invasive ability of the si CMKLR1 group was significantly lower than that of the control group(P<0.01).Western Blot was used to detect the expression of Wnt/ ?-catenin signaling pathway proteins for si CMKLR1 and control group.The expression levels of proteins including c-Myc,cyclin D1,and MMP-7 were reduced in the si CMKLR1 group and low level CMKLR1 can also significantly reduced ?-catenin protein expression(P<0.01).Conclusion: Serum chemerin level in patients with endometrial cancer are not significantly different from normal control group,and adding chemerin has no effect on the proliferation nor migration ability of endometrial cancer cells.The protein expression level of CMKLR1 in endometrial cancer tissues is higher than that in adjacent tissues.Knock down of CMKLR1 gene can inhibit the proliferation and migration through the Wnt /?-catenin signaling pathway;... |
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