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长链非编码RNA NEAT1通过抑制miR-146b-5p表达促进人乳腺癌细胞的增殖、迁移和转移。

Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression.

作者信息

Li Songming, Hao Junwen, Hong Yun, Mai Junhao, Huang Weijun

机构信息

Department of Thyroid and Breast Surgery, Guangzhou Panyu Central Hospital, Guangzhou, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Jul 21;12:6091-6101. doi: 10.2147/CMAR.S252295. eCollection 2020.

Abstract

BACKGROUND

Breast cancer (BC) is the most commonly diagnosed cancer in women. Tumor recurrence and metastasis are the key causes of death in BC patients. Long non-coding RNA (lncRNA) is closely associated with BC progression. lncRNA nuclear-enriched abundant transcript (NEAT)1 has been reported to regulate the proliferation and mobility of several types of cancer cells. However, how lncRNA NEAT1 affects the proliferation and invasion of BC cells is not known.

METHODS

Quantitative real time-polymerase chain reaction (qRT-PCR) was used to measure expression of lncRNA NEAT1 and microRNA (miR)-146b-5p in BC tissues and cell lines. Cell Counting Kit (CCK)-8, cell colony-formation, wound-healing, and Transwell™ assays were undertaken to determine the effects of lncRNA NEAT1 and miR-146b-5p on progression of BC cells. The interaction between lncRNA NEAT1 and miR-146b-5p was examined by luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA-pulldown assays.

RESULTS

Expression of lncRNA NEAT1 was upregulated in BC tissues and cell lines. High expression of lncRNA NEAT1 predicted poor overall survival in BC patients. Silencing of expression of lncRNA NEAT1 inhibited epithelial-mesenchymal transition (EMT) and suppressed the proliferation, migration and invasion of BC cells. Ectopic expression of lncRNA NEAT1 induced EMT and promoted BC progression. Mechanistic investigations revealed that miR-146b-5p was a direct target of lncRNA NEAT1, and its expression was correlated negatively with expression of lncRNA NEAT1 in BC tissues.

CONCLUSION

lncRNA NEAT1 could (i) serve as a novel prognostic marker for BC and (ii) be a potential therapeutic target for BC.

摘要

背景

乳腺癌(BC)是女性中最常被诊断出的癌症。肿瘤复发和转移是BC患者死亡的主要原因。长链非编码RNA(lncRNA)与BC进展密切相关。据报道,lncRNA核富集丰富转录本(NEAT)1可调节多种类型癌细胞的增殖和迁移。然而,lncRNA NEAT1如何影响BC细胞的增殖和侵袭尚不清楚。

方法

采用定量实时聚合酶链反应(qRT-PCR)检测BC组织和细胞系中lncRNA NEAT1和微小RNA(miR)-146b-5p的表达。采用细胞计数试剂盒(CCK)-8、细胞集落形成、伤口愈合和Transwell™实验来确定lncRNA NEAT1和miR-146b-5p对BC细胞进展的影响。通过荧光素酶报告基因、RNA结合蛋白免疫沉淀(RIP)和RNA下拉实验检测lncRNA NEAT1与miR-146b-5p之间的相互作用。

结果

lncRNA NEAT1在BC组织和细胞系中表达上调。lncRNA NEAT1高表达预示着BC患者的总生存期较差。lncRNA NEAT1表达沉默可抑制上皮-间质转化(EMT),并抑制BC细胞的增殖、迁移和侵袭。lncRNA NEAT1的异位表达诱导EMT并促进BC进展。机制研究表明,miR-146b-5p是lncRNA NEAT1的直接靶点,其表达与BC组织中lncRNA NEAT1的表达呈负相关。

结论

lncRNA NEAT1(i)可作为BC的一种新型预后标志物,(ii)可能是BC的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19ab/7382757/523a4498ab23/CMAR-12-6091-g0001.jpg

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