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微小RNA-126通过靶向表皮生长因子样蛋白7(EGFL7)、影响上皮-间质转化及细胞外调节蛋白激酶/丝裂原活化蛋白激酶(ERK/MAPK)信号通路发挥卵巢癌抗肿瘤作用。

MicroRNA-126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial-to-mesenchymal transition and ERK/MAPK signaling pathway.

作者信息

Zhang Yuhua, Qin Xiaobo, Jiang Juan, Zhao Wenjie

机构信息

Reproductive Medicine Centre, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.

Department of Obstetrics and Gynecology, Zhangqiu District Maternal and Child Health Care Hospital, Jinan, Shandong 250200, P.R. China.

出版信息

Oncol Lett. 2020 Aug;20(2):1327-1335. doi: 10.3892/ol.2020.11687. Epub 2020 May 29.

DOI:10.3892/ol.2020.11687
PMID:32724375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7377137/
Abstract

Ovarian cancer (OC) is a common gynecological malignant carcinoma worldwide. Accumulating research has revealed that multiple microRNAs (miRNAs) are abnormally expressed at different levels in various malignancies, playing vital roles in tumorigenesis. This study investigated the regulatory functions and potential mechanism of miR-126 in OC proliferation, invasion and migration. It was found that miR-126 was prominently downregulated in OC. Moreover, the decrease of miR-126 promoted the aggressive phenotypes and indicated poor prognosis of OC patients. Functional assays demonstrated that restoration of miR-126 dramatically repressed OC cell proliferation, migration and invasion. Furthermore, luciferase reporter assay was conducted to verify putative binding sites of miR-126 in the epidermal growth factor-like domain 7 (EGFL7) 3 untranslated region (3'UTR), indicating that EGFL7 was a target gene of miR-126 in OC cells. It was further discovered that miR-126 exerts its function on regulating ERK/MAPK pathway and epithelial-to-mesenchymal transition (EMT) in OC cells. The above findings suggested that miR-126 served as a cancer suppressor in OC, suggesting a promising application of miR-126 in the clinical diagnosis and therapeutics of OC.

摘要

卵巢癌(OC)是全球常见的妇科恶性肿瘤。越来越多的研究表明,多种微小RNA(miRNA)在各种恶性肿瘤中均有不同程度的异常表达,在肿瘤发生过程中发挥着至关重要的作用。本研究探讨了miR-126在OC增殖、侵袭和迁移中的调控作用及潜在机制。研究发现,miR-126在OC中显著下调。此外,miR-126的降低促进了OC的侵袭性表型,并提示OC患者预后不良。功能试验表明,恢复miR-126可显著抑制OC细胞的增殖、迁移和侵袭。此外,通过荧光素酶报告基因试验验证了miR-126在表皮生长因子样结构域7(EGFL7)3'非翻译区(3'UTR)的假定结合位点,表明EGFL7是OC细胞中miR-126的靶基因。进一步研究发现,miR-126通过调控OC细胞中的ERK/MAPK通路和上皮-间质转化(EMT)发挥其功能。上述研究结果表明,miR-126在OC中作为一种抑癌基因发挥作用,提示miR-126在OC的临床诊断和治疗中具有广阔的应用前景。

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本文引用的文献

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MicroRNA-126 expression in the peripheral white blood cells of patients with breast and ovarian cancer is a potential biomarker for the early prediction of cancer risk in the carriers of methylated .乳腺癌和卵巢癌患者外周血白细胞中MicroRNA-126的表达是甲基化携带者癌症风险早期预测的潜在生物标志物。
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