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环状 ANXA7 通过 miR-331/LAD1 轴促进肺腺癌进展。

circ-ANXA7 facilitates lung adenocarcinoma progression via miR-331/LAD1 axis.

作者信息

Wang Yu

机构信息

Department of Medical Laboratory, Zhumadian City Central Hospital, No. 747 Zhonghua Avenue, Yicheng District, Zhumadian, 463000, Henan, China.

出版信息

Cancer Cell Int. 2021 Feb 3;21(1):85. doi: 10.1186/s12935-021-01791-5.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, with a poor prognosis. The roles of circular RNAs (circRNAs) in tumors have been initially clarified. In this study, we probed into the functions and underlying molecular mechanisms of circ-ANXA7 in LUAD.

METHODS

According to circRNA microarray analysis based on 40 pairs of LUAD tissues and non-tumor tissues, a novel circ-ANXA7 was up-regulated in LUAD, which was verified in LUAD tissues and cells by RT-qPCR. Correlation between its expression and clinical features of LUAD was analyzed. When transfected with sh-circ-ANXA7, proliferation, invasion, and migration of LUAD cells were determined by a series of functional assays. Furthermore, tumor growth was investigated in nude mice injected with sh-circ-ANXA7. Dual luciferase report and gain and loss assays were used to confirm the relationships between circ-ANXA7 and miR-331, miR-331 and LAD1.

RESULTS

circ-ANXA7 was up-regulated in LUAD tissues and cells. Its high expression promoted proliferation, migration, and invasion of LUAD cells as well as tumor growth. High circ-ANXA7 expression usually predicted a poorer prognosis for LUAD patients. Furthermore, circ-ANXA7 could accelerate proliferation and invasion of LUAD cells by targeting miR-331. miR-331 directly bound to the 3'-UTR of LAD1. LAD1 induced proliferation and invasion of LUAD cells, which was reversed after co-transfection with circ-ANXA7 knockdown. LAD1 expression could be an independent prognostic marker for LUAD by univariate and multivariate analysis.

CONCLUSIONS

Our research identified a novel circ-ANXA7 for LUAD, which could facilitate proliferation, migration, and invasion of LUAD cells by miR-331/ LAD1 axis. circ-ANXA7 could become a promising prognosis and treatment target for LUAD.

摘要

背景

肺腺癌(LUAD)是肺癌最常见的组织学亚型,预后较差。环状RNA(circRNA)在肿瘤中的作用已初步明确。在本研究中,我们探究了circ-ANXA7在LUAD中的功能及潜在分子机制。

方法

基于40对LUAD组织和非肿瘤组织进行circRNA微阵列分析,发现一种新的circ-ANXA7在LUAD中上调,并通过RT-qPCR在LUAD组织和细胞中进行验证。分析其表达与LUAD临床特征的相关性。转染sh-circ-ANXA7后,通过一系列功能实验检测LUAD细胞的增殖、侵袭和迁移能力。此外,对注射sh-circ-ANXA7的裸鼠进行肿瘤生长研究。采用双荧光素酶报告基因实验及过表达和敲低实验来证实circ-ANXA7与miR-331、miR-331与LAD1之间的关系。

结果

circ-ANXA7在LUAD组织和细胞中上调。其高表达促进了LUAD细胞的增殖、迁移和侵袭以及肿瘤生长。circ-ANXA7高表达通常预示LUAD患者预后较差。此外,circ-ANXA7可通过靶向miR-331促进LUAD细胞的增殖和侵袭。miR-331直接与LAD1的3'-UTR结合。LAD1诱导LUAD细胞的增殖和侵袭,与circ-ANXA7敲低共转染后这种作用被逆转。单因素和多因素分析显示,LAD1表达可能是LUAD的独立预后标志物。

结论

我们的研究发现了一种新的LUAD相关circ-ANXA7,其可通过miR-331/LAD1轴促进LUAD细胞的增殖、迁移和侵袭。circ-ANXA7有望成为LUAD有前景的预后和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8a7/7860208/746971a7edd5/12935_2021_1791_Fig1_HTML.jpg

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