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.
J Cell Mol Med. 2020 Apr;24(7):4127-4135. doi: 10.1111/jcmm.15069. Epub 2020 Feb 19.
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.
子宫内膜癌是最常见的妇科恶性肿瘤之一，也是女性癌症相关死亡的第六大主要原因。在这里，我们定义了 circ_0000043（以下简称 circ_PUM1）在子宫内膜癌发生和发展中的作用和分子机制。实时定量 PCR 用于检测正常子宫内膜组织和子宫内膜癌组织中 circ_PUM1 的表达。circ_PUM1 过表达或敲低后，观察裸鼠细胞功能和肿瘤发生的变化。生物信息学分析和双荧光素酶报告基因检测用于预测和分析 circ_PUM1 结合的 miRNAs。使用 Western blot 分析基因表达变化。circ_PUM1 在子宫内膜癌组织中的表达明显高于正常组织。circ_PUM1 的上调促进了子宫内膜癌细胞的增殖、迁移和侵袭。circ_PUM1 敲低则观察到相反的结果，circ_PUM1 敲低后的子宫内膜癌细胞的肿瘤发生能力与对照细胞相比降低。circ_PUM1 能够与 miR-136 结合，并上调其靶基因 NOTCH3，而过表达 miR-136 可以逆转这一作用。circ_PUM1 可以与 miR-136 竞争，导致 NOTCH3 的上调，从而促进子宫内膜癌的发展。
