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NEAT1 通过调节 miR-448 和 ZEB1 促进乳腺癌的进展。

NEAT1 contributes to breast cancer progression through modulating miR-448 and ZEB1.

机构信息

Center of Reproductive Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, China.

Department of Breast Surgery, The Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China.

出版信息

J Cell Physiol. 2018 Nov;233(11):8558-8566. doi: 10.1002/jcp.26470. Epub 2018 May 15.

Abstract

Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF-7, MDA-MB-453, MDA-MB-231, and SKBR3 cells compared to normal mammary epithelial cells MCF-10A while miR-448 was decreased. We found that downregulation of NEAT1 was able to inhibit the growth of breast cancer cells and miR-448 mimic exerted the similar function. Bioinformatics analysis and dual luciferase reporter assays confirmed the negative correlation between NEAT1 and miR-448 in vitro. In addition, ZEB1 was predicted as a novel mRNA target of miR-448. Overexpression of NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting miR-448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1 levels while miR-448 mimic can repress ZEB1. It was speculated in our study that NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by sponging miR-448 in breast cancer. To conclude, we uncovered that NEAT1 participated in breast cancer progression by regulating miR-448 and ZEB1. NEAT1 can be provided as a vital biomarker in breast cancer diagnosis and treatment therapy.

摘要

乳腺癌是一种常见的女性癌症。越来越多的证据表明,长链非编码 RNA(lncRNA)在乳腺癌中发挥着关键作用。迄今为止,lncRNA 在乳腺癌中的作用机制仍未得到很好的阐明。在我们目前的研究中,我们专注于长链非编码 RNA 核丰富丰富转录物 1(NEAT1)在乳腺癌中的生物学作用。我们观察到,与正常乳腺上皮细胞 MCF-10A 相比,人乳腺癌细胞 MCF-7、MDA-MB-453、MDA-MB-231 和 SKBR3 细胞中 NEAT1 水平显著升高,而 miR-448 则降低。我们发现下调 NEAT1 能够抑制乳腺癌细胞的生长,而 miR-448 模拟物则发挥类似的功能。生物信息学分析和双荧光素酶报告基因实验证实了体外 NEAT1 和 miR-448 之间的负相关关系。此外,ZEB1 被预测为 miR-448 的一种新型 mRNA 靶标。过表达 NEAT1 可以通过抑制 miR-448 和上调 ZEB1 诱导乳腺癌细胞生长、迁移和侵袭。研究表明,NEAT1 可以增加 ZEB1 水平,而 miR-448 模拟物可以抑制 ZEB1。我们推测,在乳腺癌中,NEAT1 可以作为竞争性内源性 lncRNA(ceRNA)通过海绵吸附 miR-448 来调节 ZEB1。总之,我们揭示了 NEAT1 通过调节 miR-448 和 ZEB1 参与乳腺癌的进展。NEAT1 可以作为乳腺癌诊断和治疗的重要生物标志物。

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