Circ_PUM1 promotes the development of endometrial cancer by targeting the miR-136/NOTCH3 pathway
Circ_PUM1 promotes the development of endometrial cancer by targeting the miR-136/NOTCH3 pathway
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Circ_PUM1通过靶向miR-136/NOTCH3通路促进子宫内膜癌的发展
DOI：
10.1111/jcmm.15069
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发表时间：
2020-02-19
影响因子：
5.3
通讯作者：
Zhao, Yang
中科院分区：
文献类型：
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作者：
Zong, Zhi-Hong;Liu, Yao;Zhao, Yang
子宫内膜癌是最常见的妇科恶性肿瘤之一，也是妇女癌症相关死亡的第六大常见原因。在此，我们明确了circ_0000043（以下简称circ_CR1）在子宫内膜癌发生发展中的作用及其分子机制。采用定量逆转录-聚合酶链反应（QRT-PCR）检测正常子宫内膜组织和子宫内膜癌组织中circ_1的表达。在circ_resist1过表达或敲低后，检测细胞功能和裸鼠成瘤性的变化。采用生物信息学分析和双荧光素酶报告基因分析方法预测和分析circ_b1结合的miRNAs。使用Western印迹分析基因表达变化。Circ_1在子宫内膜癌组织中的表达水平显著高于正常组织。cycl_1表达上调促进子宫内膜癌细胞的增殖、迁移和侵袭。在circ_resist1敲低的情况下观察到相反的结果，并且与对照细胞相比，circ_resist1敲低后子宫内膜癌细胞的致瘤能力降低。Circ_CRP1能够与miR-136结合，并上调其靶基因NOTCH 3，这可以通过miR-136的过表达来逆转。Circ_CRP1可以与miR-136竞争，导致NOTCH 3上调，从而促进子宫内膜癌的发生。
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.