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长链非编码RNA HOXA-AS2通过靶向miR-885-5p/RBBP4轴促进胶质母细胞瘤的发生。

LncRNA HOXA-AS2 promotes glioblastoma carcinogenesis by targeting miR-885-5p/RBBP4 axis.

作者信息

Shou Jixin, Gao Haidong, Cheng Sen, Wang Bingbing, Guan Haibo

机构信息

Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Erqi District, No. 3 Kangfu Front Street, Zhengzhou, 450052, Henan, China.

出版信息

Cancer Cell Int. 2021 Jan 11;21(1):39. doi: 10.1186/s12935-020-01690-1.

DOI:10.1186/s12935-020-01690-1
PMID:33430870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7798264/
Abstract

BACKGROUND

LncRNA HOXA-AS2 has been found in the literature to deteriorate glioblastoma. However, its regulatory mechanism is yet to be fully investigated. Our study focused chiefly on the interaction and role of the HOXA-AS2/miR-885-5p/RBBP4 axis in the development of glioblastoma.

METHODS

qRT-PCR analysis was performed to detect the expression of lncRNA, miRNA and mRNA in glioblastoma tissues and cells. Dual-luciferase assay, RIP assay and RNA pull-down assay were later carried out to reveal the interactions among HOXA-AS2, miR-885-5p and RBBP4. After that, CCK-8 assay, BrdU assay, nude mice xenografting assay, western blot assay, and flow cytometry were carried out to analyze the effect of the HOXA-AS2/miR-885-5p/RBBP4 axis on glioblastoma samples.

RESULTS

HOXA-AS2 and RBBP4 were found to be overexpressed in glioblastoma. Experimental results showed that HOXA-AS2 and RBBP4 contributed to the tumorigenesis of glioblastoma cells. However, miR-885-5p was observed to be downregulated in glioblastoma. Findings also indicated that HOXA-AS2 could negatively regulate miR-885-5p, thereby enhancing RBBP4 expression.

CONCLUSION

Overall, HOXA-AS2 promoted the tumorigenesis of glioblastoma by targeting and regulating miR-885-5p to induce the expression of RBBP4.

摘要

背景

文献中已发现长链非编码RNA HOXA-AS2会使胶质母细胞瘤恶化。然而,其调控机制尚未得到充分研究。我们的研究主要聚焦于HOXA-AS2/miR-885-5p/RBBP4轴在胶质母细胞瘤发生发展中的相互作用及作用机制。

方法

采用qRT-PCR分析检测胶质母细胞瘤组织和细胞中长链非编码RNA、微小RNA和信使核糖核酸的表达。随后进行双荧光素酶报告基因检测、RNA免疫沉淀检测和RNA下拉检测,以揭示HOXA-AS2、miR-885-5p和RBBP4之间的相互作用。在此之后,进行CCK-8检测、BrdU检测、裸鼠异种移植检测、蛋白质免疫印迹检测和流式细胞术,以分析HOXA-AS2/miR-885-5p/RBBP4轴对胶质母细胞瘤样本的影响。

结果

发现HOXA-AS2和RBBP4在胶质母细胞瘤中高表达。实验结果表明,HOXA-AS2和RBBP4促进了胶质母细胞瘤细胞的肿瘤发生。然而,观察到miR-885-5p在胶质母细胞瘤中表达下调。研究结果还表明,HOXA-AS2可负向调节miR-885-5p,从而增强RBBP4的表达。

结论

总体而言,HOXA-AS2通过靶向调控miR-885-5p诱导RBBP4表达,促进了胶质母细胞瘤的肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/11a313cb5466/12935_2020_1690_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/11a313cb5466/12935_2020_1690_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/2dd6d8d099e8/12935_2020_1690_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/553f079584e6/12935_2020_1690_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/7b06b856d40d/12935_2020_1690_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/c20267892518/12935_2020_1690_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/fa7f8c485d33/12935_2020_1690_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4db/7798264/11a313cb5466/12935_2020_1690_Fig10_HTML.jpg

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