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LncRNA XIST 通过竞争性结合 miR-200a 上调 Fus 从而加速宫颈癌进展。

LncRNA XIST accelerates cervical cancer progression via upregulating Fus through competitively binding with miR-200a.

机构信息

Department of Obstetrics and Gynecology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No.1665, KongJiang Road, YangPu District, Shanghai, 200092, China.

Department of Obstetrics and Gynecology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, No.1665, KongJiang Road, YangPu District, Shanghai, 200092, China.

出版信息

Biomed Pharmacother. 2018 Sep;105:789-797. doi: 10.1016/j.biopha.2018.05.053. Epub 2018 Jun 15.

Abstract

As one of the commonest gynecological malignancies in the world, cervical cancer brings great threat for public health. Long non-coding RNAs (LncRNAs) have been proved to be closely related to the progression of various cancers, including cervical cancer. As a tumor promoter, lncRNA XIST has been reported in various malignant tumors. In this study, we aim to explore the specific mechanism and biological function of XIST in cervical cancer. At first, the expression levels of XIST were examined in both tissues and cell lines with qRT-PCR. XIST was extremely overexpressed in cervical cancer tissues and cell lines. Kaplan Meier method was then applied to analyze the correlation between XIST expression and overall survival of cervical cancer patients. Loss-of- function assays were designed and conducted to verify the oncogenic function of XIST on cervical cancer progression. Additionally, the results of mechanistic experiments indicated that XIST upregulated Fus through competitively binding with miR-200a. Finally, rescue assays were conducted to demonstrate the regulatory function of XIST-miR-200a-Fus axis in cervical cancer progression. Collectively, XIST served as a ceRNA in cervical cancer progression through modulating miR-200a/Fus axis.

摘要

作为世界上最常见的妇科恶性肿瘤之一,宫颈癌对公众健康构成了巨大威胁。长链非编码 RNA(lncRNA)已被证明与包括宫颈癌在内的各种癌症的进展密切相关。lncRNA XIST 作为一种肿瘤促进物,已在各种恶性肿瘤中被报道。在这项研究中,我们旨在探讨 XIST 在宫颈癌中的具体作用机制和生物学功能。首先,我们通过 qRT-PCR 检测了 XIST 在组织和细胞系中的表达水平。结果显示,XIST 在宫颈癌组织和细胞系中呈高度过表达。然后,我们采用 Kaplan-Meier 方法分析了 XIST 表达与宫颈癌患者总生存期的相关性。接着,我们设计并进行了功能丧失实验,以验证 XIST 对宫颈癌进展的致癌作用。此外,机制实验的结果表明,XIST 通过与 miR-200a 竞争结合来上调 Fus。最后,我们进行了挽救实验,以证明 XIST-miR-200a-Fus 轴在宫颈癌进展中的调节作用。综上所述,XIST 通过调节 miR-200a/Fus 轴在宫颈癌进展中发挥 ceRNA 的作用。

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