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长链非编码RNA IGBP1-AS1/miR-24-1/ZIC3环状结构调控乳腺癌的增殖和侵袭能力。

LncRNA IGBP1-AS1/miR-24-1/ZIC3 loop regulates the proliferation and invasion ability in breast cancer.

作者信息

Chen Deqin, Fan Yangfan, Wan Fang

机构信息

Department of Surgery, The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang China.

出版信息

Cancer Cell Int. 2020 May 7;20:153. doi: 10.1186/s12935-020-01214-x. eCollection 2020.

DOI:10.1186/s12935-020-01214-x
PMID:32390766
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7203854/
Abstract

BACKGROUND

Breast cancer (BC) is one of the malignant solid tumors with the highest morbidity in the world. Currently, the therapeutic outcome of different types of treatment can be unsatisfactory. Novel lncRNA biomarkers in BC remains to be further explored.

METHODS

Different expression of lncRNAs among BC tissues and adjacent normal tissues were identified with microarray analyses. A series of in vivo and in vitro gain-of-function laboratory procedures were conducted to study the biological functions of IGBP1-AS1. The prognostic effects on IGBP1-AS1 survival were evaluated by using in situ hybridization and survival analysis. In addition, other experiments including RNA pull down analysis, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation as well as validating assays conducted in vivo were applied to identify the target and regulatory mechanisms of IGBP1-AS1.

RESULTS

Significant down-regulation of IGBP1-AS1 was discovered in the cell lines and tissues of BC. With respect to its biological function, overexpression of IGBP1-AS1 had inhibitory effects on the invasion and proliferation of BC cells in vivo as well as in vitro. Analysis of the samples obtained from BC patients indicated a positive effect of IGBP1-AS1 on survival outcomes. LncRNA IGBP1-AS1/miR-24-1/ZIC3 axis as a loop can regulate the proliferation and invasion of BC cells.

CONCLUSIONS

IGBP1-AS1 could have inhibitory impact on the invasion and proliferation of BC and may serve as a promising biomarker for BC.

摘要

背景

乳腺癌(BC)是全球发病率最高的恶性实体肿瘤之一。目前,不同类型治疗的疗效可能不尽人意。BC中新型长链非编码RNA(lncRNA)生物标志物仍有待进一步探索。

方法

通过微阵列分析确定BC组织和相邻正常组织中lncRNAs的差异表达。进行了一系列体内和体外功能获得性实验室操作,以研究IGBP1-AS1的生物学功能。通过原位杂交和生存分析评估IGBP1-AS1对生存的预后影响。此外,还应用了其他实验,包括RNA下拉分析、RNA免疫沉淀、荧光素酶报告基因检测、染色质免疫沉淀以及体内验证实验,以确定IGBP1-AS1的靶标和调控机制。

结果

在BC的细胞系和组织中发现IGBP1-AS1显著下调。就其生物学功能而言,IGBP1-AS1的过表达在体内和体外均对BC细胞的侵袭和增殖具有抑制作用。对BC患者样本的分析表明IGBP1-AS1对生存结果有积极影响。LncRNA IGBP1-AS1/miR-24-1/ZIC3轴作为一个环,可以调节BC细胞的增殖和侵袭。

结论

IGBP1-AS1可能对BC的侵袭和增殖具有抑制作用,并可能成为BC有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/7706c13ab2f2/12935_2020_1214_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/d49eeea1b271/12935_2020_1214_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/6c04a3867309/12935_2020_1214_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/15f4253da092/12935_2020_1214_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/277758469f1e/12935_2020_1214_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/cef531c0c6bd/12935_2020_1214_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/7706c13ab2f2/12935_2020_1214_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/d49eeea1b271/12935_2020_1214_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/6c04a3867309/12935_2020_1214_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/15f4253da092/12935_2020_1214_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/277758469f1e/12935_2020_1214_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/cef531c0c6bd/12935_2020_1214_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6405/7203854/7706c13ab2f2/12935_2020_1214_Fig6_HTML.jpg

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