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运动神经元和胰腺同源盒 1（MNX1）通过调节细胞周期蛋白 E 促进宫颈鳞癌增殖。

Motor Neuron and Pancreas Homeobox 1 (MNX1) Is Involved in Promoting Squamous Cervical Cancer Proliferation via Regulating Cyclin E.

机构信息

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland).

Department of Obstetrics and Gynaecology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei, China (mainland).

出版信息

Med Sci Monit. 2019 Aug 22;25:6304-6312. doi: 10.12659/MSM.914233.

DOI:10.12659/MSM.914233
PMID:31436258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6716296/
Abstract

BACKGROUND Cervical cancer is one of the most lethal gynecologic malignancies worldwide. The objective of this study was to assess the role of MNX1 in cervical cancer and its underlying mechanisms. MATERIAL AND METHODS The expression of motor neuron and pancreas homeobox 1 (MNX1) in immortal epithelial cervical cell line ECT, cervical cancer cell HeLa, and SiHa and cervical cancer, as well as in adjacent noncancer tissues, was detected and analyzed. CCK-8 and colony formation assays were performed to evaluate the effects of MNX1 overexpression on cervical cancer cell proliferation. Transwell assay was used to detect migration and invasion after MNX1 knockdown or overexpression. Real-time PCR and Western blotting were used to examine MNX1 and cell cycle regulator expression. RESULTS Data from our study indicated that MNX1 was upregulated both in cervical cancer cell lines and cervical cancer tissues. The high levels of MNX1 are related to advanced stages and lymph nodes metastasis. The overexpression of MNX1 promoted cervical cancer cells proliferation, migration, and invasion. Moreover, MNX1 upregulated 2 critical cell cycle regulators, CCNE1 and CCNE2. CONCLUSIONS These findings reveal MNX1 as a novel oncogene of cervical cancer and indicate MNX1 is a promising therapeutic and prognostic biomarker.

摘要

背景

宫颈癌是全球致死率最高的妇科恶性肿瘤之一。本研究旨在评估 MNX1 在宫颈癌中的作用及其潜在机制。

方法

检测并分析永生化宫颈上皮细胞系 ECT、宫颈癌 HeLa 和 SiHa 细胞及宫颈癌组织和相应癌旁组织中运动神经元和胰腺同源盒 1（MNX1）的表达。通过 CCK-8 和集落形成实验评估 MNX1 过表达对宫颈癌细胞增殖的影响。通过 Transwell 实验检测 MNX1 敲低或过表达后迁移和侵袭的变化。采用实时 PCR 和 Western blot 检测 MNX1 和细胞周期调控因子的表达。

结果

本研究数据表明，MNX1 在宫颈癌细胞系和宫颈癌组织中均上调。MNX1 的高表达与晚期和淋巴结转移有关。MNX1 的过表达促进了宫颈癌细胞的增殖、迁移和侵袭。此外，MNX1 上调了 2 个关键的细胞周期调控因子 CCNE1 和 CCNE2。

结论

这些发现揭示了 MNX1 是宫颈癌的一种新型癌基因，并表明 MNX1 是一种有前途的治疗和预后生物标志物。

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