Chemerin/CMKLR1 Axis Induces Proliferation and Invasion in Human Endometrial Cancer

Abstract Objectives: This study aimed to analyze the differences in the chemokine chemerin and its receptor chemokine-like receptor 1 (CMKLR1) between endometrial cancer (EC) patients and normal populations, and investigate the effect of CMKLR1 on the proliferation, migration and invasion of HEC-1B cells and its roles in Wnt/ β-catenin signaling pathways. Methods: The clinical data of 50 EC cases (study group) admitted from January 2018 to December 2020 were collected, and 50 cases of those who underwent a health checkup in Tianjin Central Hospital of Gynecology and Obstetrics during the same period were selected and included in the control group. The relationship between serum chemerin levels and clinicopathological features, as well as the difference in CMKLR1 protein expression between cancer and para-carcinoma tissue were compared. RT-PCR and Western blot methods were adopted to detect CMKLR1 expression in different EC cell lines and normal endometrial cells. CMKLR1 shRNA and NC shRNA stably transfected cell lines were constructed by shRNA interference technology to verify the interference efficiency. CCK-8 count assay, cell scratch test and transwell chamber were used to detect the effects of silencing CMKLR1 gene expression on the proliferation, migration and invasion of EC cells. Changes in Wnt/β-catenin signaling pathways were detected after silencing CMKLR1 gene expression by Western blot. Results:The ELISA showed that the serum chemerin level in EC group was higher than that in normal control group. In EC group, the serum chemerin level in advanced-stage patients was higher than that in early-stage patients (P < 0.05). Immunohistochemistry showed that the CMKLR1 expression in EC tissue was higher than that in paracarcinoma tissue. Cytological findings showed that CMKLR1 expression was the highest in HEC-1B compared with normal endometrial cells (NE) and EC cell lines HEC-1A and Ishikawa, and the silencing efficiency of CMKLR1 gene in HEC-1B cells treated by shRNA interference technology reached 70%. CCK-8 assay showed that silencing CMKLR1 gene expression can significantly reduce the proliferation rate of HEC-1B cells (P < 0.05). The scratch test showed that silencing CMKLR1 expression genes significantly inhibit the migration of HEC-1B cells (P < 0.05). Transwell chamber showed that silencing CMKLR1 gene expression can inhibit the invasion ability of HEC-1B cells (P < 0.05). Western blot detection showed that silencing CMKLR1 gene expression can significantly inhibit the protein expression of phosphorylated β-catenin and cyclin D1 protein in HEC-1B cells, and the difference was statistically significant (P < 0.05). Conclusion: The chemokine chemerin and its receptor CMKLR1 may be involved in the progression and metastasis of EC. Serum chemerin levels can be used as a molecular marker for early diagnosis of EC, and CMKLR1 gene can provide a new target for the potential gene therapy of EC.