GSE167548
Expression profile of transcripts associated with Apcin-induced growth inhibition and apoptosis in endometrial carcinoma
Background: Endometrial carcinoma (EC) is a common gynecological malignancy with increasing incidence and death rate during the past years. In order to obtain better prognosis, it is necessary to develop novel therapy strategies for EC, especially for molecular targeted therapy. CDC20 is an Anaphase promoting complex/cyclosome (APC/C) activator and has been reported to exhibit an oncogenic function. Thus, CDC20 could be a promising therapeutic target for EC.  Methods: The expression of CDC20 was analyzed based on TCGA databases and Human Protein Atlas and verified in EC cell lines by western blotting. We evaluated the anti-tumor effects of CDC20 inhibitor Apcin on proliferation, apoptosis, cell cycle and mobility of EC cell lines, AN3CA and KLE, by CCK8 assay, flow cytometer analysis, wound healing and transwell assay respectively. Furthermore, we performed RNA-sequencing on EC cells with or without Apcin treatment and conducted bioinformatics analysis to explore the molecular mechanism. The differentially expressed genes were verified by PCR and western blotting.  Results: TCGA data reveal that the expression level of CDC20 is higher in EC tissue than in nonmalignant tissue. Stable and high expression of CDC20 was also detected in EC cell lines. Treatment with CDC20 inhibitor Apcin inhibited proliferation and induced apoptosis while did not influence mobility ability of EC cells. The effects of Apcin treatment on cell cycle distribution were different between these two EC cell lines. The percentage of G2/M phase cells was increased in Apcin-treated KLE cells but did not change significantly in Apcin-treated AN3CA cells. Bioinformatics analysis of RNA-seq data identified that apoptosis, P53 pathway and TNF signaling pathway were activated in EC cells after Apcin treatment, indicating the potential mechanisms through which Apcin exerted its antitumor function. Furthermore, the anti-tumor effects of Apcin are related to the regulation of BBC3 and P21 expression in EC cells.  Conclusions: CDC20 is a promising molecular target and Apcin may be a potential pharmaceutics for EC treatment. CDC20 is a novel molecular target in EC, which highlights Apcin as a candidate drug in targeted therapy of EC. Overall design: RNA-sequencing on EC cell lines (AN3CA and KLE) with or without Apcin treatment