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微小 RNA-1297 通过靶向宫颈癌中的 AEG-1 抑制转移和上皮-间充质转化。

MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by targeting AEG-1 in cervical cancer.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

Medical Examination Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

出版信息

Oncol Rep. 2017 Nov;38(5):3121-3129. doi: 10.3892/or.2017.5979. Epub 2017 Sep 20.

Abstract

Accumulating evidence has demonstrated that aberrant miRNAs contribute to cervical cancer (CC) development and progression. However, the roles of various miRNAs in CC remain to be determined. In the present study, we confirmed that a decreased miR-1297 expression was present in CC tissues and cell lines. Our clinical analysis revealed that the downregulated miR-1297 expression was significantly correlated with poor prognostic features including lymph node metastasis and lymphovascular space invasion. Moreover, we confirmed that miR-1297 was a novel independent prognostic marker for predicting the 5-year survival of CC patients. The ectopic overexpression of miR-1297 inhibited cell migration, invasion and EMT progression, while downregulated miR-1297 reversed these effects. In addition, miR-1297 regulated AEG-1 by directly binding to its 3'-UTR. In clinical samples of CC, miR-1297 was inversely correlated with AEG-1, which was upregulated in CC. Alteration of AEG-1 expression at least partially abolished the migration, invasion and EMT progression effects of miR-1297 on CC cells. In conclusion, our results indicated that miR-1297 functioned as a tumor suppressor gene in regulating the EMT and metastasis of CC via targeting of AEG-1, and may represent a novel potential therapeutic target and prognostic marker for CC.

摘要

越来越多的证据表明,异常表达的 miRNA 参与了宫颈癌(CC)的发生和发展。然而,各种 miRNA 在 CC 中的作用仍有待确定。在本研究中,我们证实 miR-1297 在 CC 组织和细胞系中的表达降低。临床分析显示,miR-1297 的下调表达与不良预后特征显著相关,包括淋巴结转移和脉管侵犯。此外,我们证实 miR-1297 是预测 CC 患者 5 年生存率的一个新的独立预后标志物。miR-1297 的异位过表达抑制了细胞迁移、侵袭和 EMT 进展,而下调 miR-1297 则逆转了这些效应。此外,miR-1297 通过直接结合其 3'-UTR 调控 AEG-1 的表达。在 CC 的临床样本中,miR-1297 与 AEG-1 呈负相关,而 AEG-1 在 CC 中上调。改变 AEG-1 的表达至少部分消除了 miR-1297 对 CC 细胞迁移、侵袭和 EMT 进展的影响。总之,我们的研究结果表明,miR-1297 通过靶向 AEG-1 作为肿瘤抑制基因,在调节 CC 的 EMT 和转移中发挥作用,可能代表了 CC 潜在的治疗靶点和预后标志物。

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