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miRNA-199b-3p 通过靶向 ZEB1 抑制 CHK1/E-钙黏蛋白/EMT 信号通路来抑制卵巢癌细胞的生长和进展。

miRNA‑199b‑3p suppresses growth and progression of ovarian cancer via the CHK1/E‑cadherin/EMT signaling pathway by targeting ZEB1.

机构信息

Department of Gynecology and Obstetrics, Weihai Municipal Hospital, Shandong University, Weihai, Shandong 264200, P.R. China.

出版信息

Oncol Rep. 2021 Feb;45(2):569-581. doi: 10.3892/or.2020.7895. Epub 2020 Dec 11.

Abstract

Ovarian cancer is one of the most common gynecological malignancies and its pathogenesis and progression are regulated by multiple genes. MicroRNAs (miRNAs) are endogenous non‑coding RNAs that regulate body function by altering post‑transcriptional gene expression. Previous studies have suggested that miRNAs are closely associated with the pathogenesis and progression of several malignancies, including breast cancer, hepatocellular carcinoma and glioma, among others. Therefore, miRNAs are promising novel targets for the diagnosis, treatment and determination of prognostic factors in patients with ovarian cancer. In the present study, the role of miRNA‑133b‑3p in ovarian cancer progression and its possible mechanism of action were investigated. The results demonstrated that the expression of miRNA‑199b‑3p and zinc finger E‑box binding homeobox (ZEB)1 were increased in patients with ovarian cancer. The overall survival (OS) and disease‑free survival (DFS) of patients with ovarian cancer and high miRNA‑199b‑3p expression were prolonged compared with those of patients with low miRNA‑199b‑3p expression. Additionally, the OS and DFS of patients with ovarian cancer and low ZEB1 expression were longer compared with those of patients with high ZEB1 expression. Furthermore, miRNA‑199b‑3p overexpression reduced cell proliferation and promoted apoptosis in an in vitro model of ovarian cancer. miRNA‑199b‑3p overexpression also suppressed ZEB1 and checkpoint kinase 1 expression and induced E‑cadherin expression and epithelial‑to‑mesenchymal transition in this model. Furthermore, the effects of miRNA‑199b‑3p‑mediated apoptosis and migration were attenuated by ZEB1 and E‑cadherin, respectively. The results of the present study indicated that miRNA‑199b‑3p suppressed ovarian cancer progression by targeting ZEB1, which may represent a promising therapeutic target for ovarian cancer.

摘要

卵巢癌是最常见的妇科恶性肿瘤之一,其发病机制和进展受多种基因调控。微小 RNA(miRNA)是内源性非编码 RNA,通过改变转录后基因表达来调节机体功能。先前的研究表明,miRNA 与多种恶性肿瘤的发病机制和进展密切相关,包括乳腺癌、肝癌和脑胶质瘤等。因此,miRNA 是卵巢癌诊断、治疗和确定预后因素的有前途的新型靶点。在本研究中,研究了 miRNA-133b-3p 在卵巢癌进展中的作用及其可能的作用机制。结果表明,卵巢癌患者中 miRNA-199b-3p 和锌指 E-框结合同源盒 1(ZEB1)的表达增加。miRNA-199b-3p 高表达的卵巢癌患者的总生存期(OS)和无病生存期(DFS)长于 miRNA-199b-3p 低表达的患者。此外,ZEB1 低表达的卵巢癌患者的 OS 和 DFS 长于 ZEB1 高表达的患者。此外,miRNA-199b-3p 过表达可降低卵巢癌细胞在体外模型中的增殖并促进凋亡。miRNA-199b-3p 过表达还可抑制 ZEB1 和检查点激酶 1 的表达,并诱导上皮-间充质转化和 E-钙黏蛋白在该模型中的表达。此外,ZEB1 和 E-钙黏蛋白分别减弱了 miRNA-199b-3p 介导的凋亡和迁移的作用。本研究结果表明,miRNA-199b-3p 通过靶向 ZEB1 抑制卵巢癌进展,这可能代表了卵巢癌有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf9/7757082/b0cbfec41d24/OR-45-02-0569-g00.jpg

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