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miRNA-4465 通过直接靶向癌基因 EZH2 抑制非小细胞肺癌的肿瘤增殖和转移。

MicroRNA-4465 suppresses tumor proliferation and metastasis in non-small cell lung cancer by directly targeting the oncogene EZH2.

机构信息

Department of Critical Care Medicine, Lishui Center Hospital, Lishui, Zhejiang, 323000, China.

Department of Anesthesiology, Hubei Cancer Hospital, No 116 Zhuodaoquan South Load,Hongshan District Wuhan HuBei, China.

出版信息

Biomed Pharmacother. 2017 Dec;96:1358-1362. doi: 10.1016/j.biopha.2017.11.070. Epub 2017 Nov 21.

DOI:10.1016/j.biopha.2017.11.070
PMID:29169732
Abstract

MicroRNA-26 (miR-26) has been reported to be connected with tumor progression. MicroRNA-4465 (miR-4465) was one member of miR-26 family, however, the role of miR-4465 in non-small cell lung cancer (NSCLC) was unknown. This study was aimed to explore the function of miR-4465 and investigate whether miR-4465 can be a potential target for treating human NSCLC. QRT-PCR was applied to evaluate the miR-4465 expression levels in NSCLC cells. Then, we demonstrated the role of miR-4465 in NSCLC cells biological characteristics through detecting proliferation, migration and invasion. Luciferase reporter assay and TargetScan were applied to explore the potential target gene of miR-4465. In this study, we found that the miR-4465 expression levels in NSCLC cell lines were significantly reduced when compared to the normal human bronchial epithelial cell lines. And, over expression of miR-4465 could restrain the proliferation, migration and invasion of NSCLC. Moreover, MiR-4465 reduced EZH2 protein expression through the binding sites in 3' -UTR of the EZH2 mRNA, indicating EZH2 may be a direct target gene of miR-4465. Conclusively, miR-4465 suppressed cancer cells proliferation and metastasis by directly targeting the oncogene EZH2 and it may serve as a new potential therapeutic target in NSCLC.

摘要

miR-26 已被报道与肿瘤进展有关。miR-4465 是 miR-26 家族的一员,然而,miR-4465 在非小细胞肺癌(NSCLC)中的作用尚不清楚。本研究旨在探讨 miR-4465 的功能,并研究 miR-4465 是否可以成为治疗人类 NSCLC 的潜在靶点。qRT-PCR 用于评估 NSCLC 细胞中 miR-4465 的表达水平。然后,我们通过检测增殖、迁移和侵袭来证明 miR-4465 在 NSCLC 细胞生物学特性中的作用。荧光素酶报告基因检测和 TargetScan 用于探索 miR-4465 的潜在靶基因。在这项研究中,我们发现 NSCLC 细胞系中的 miR-4465 表达水平明显低于正常人类支气管上皮细胞系。并且,过表达 miR-4465 可以抑制 NSCLC 的增殖、迁移和侵袭。此外,miR-4465 通过 EZH2 mRNA 3' -UTR 上的结合位点降低 EZH2 蛋白表达,表明 EZH2 可能是 miR-4465 的直接靶基因。总之,miR-4465 通过直接靶向癌基因 EZH2 抑制癌细胞增殖和转移,可能成为 NSCLC 的新的潜在治疗靶点。

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