Affiliation: | 1. Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institute in Guangdong Province, Guangzhou, China;2. Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, China;3. Department of Gynecologic Oncology Research Office, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China |
Abstract: | Endometrial cancer is one of the most common gynaecological malignancies and the sixth most common cause of cancer-related death among women. Here, we define the role and molecular mechanism of circ_0000043 (hereafter referred to as circ_PUM1) in the development and progression of endometrial carcinoma. QRT-PCR was used to detect the expression of circ_PUM1 in normal endometrial tissue and endometrial carcinoma tissues. Changes in cell function and tumorigenicity in nude mice were examined after circ_PUM1 overexpression or knockdown. Bioinformatic analysis and dual-luciferase reporter assay were used to predict and analyse the miRNAs that circ_PUM1 binds. Gene expression changes were analysed using Western blot. Circ_PUM1 was expressed at significantly higher levels in endometrial cancer tissues than in normal tissues. Up-regulation of circ_PUM1 promoted the proliferation, migration and invasion of endometrial carcinoma cells. Opposite results were observed with circ_PUM1 knockdown, and the tumorigenic ability of endometrial cancer cells after circ_PUM1 knockdown was reduced compared to control cells. Circ_PUM1 is capable of binding to miR-136, and up-regulating its target gene NOTCH3, which can be reversed by overexpression of miR-136. Circ_PUM1 can compete with miR-136, leading to up-regulation of NOTCH3, and thereby promote the development of endometrial cancer. |