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Circ_0000020通过靶向miR-142-5p提高PIK3CA的表达并促进胶质瘤细胞的恶性表型。

Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p.

作者信息

Wang Xu, Zhu Yaozu

机构信息

Department of Neurosurgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Jingzhou Street No. 136, Xiangyang, 441021, Hubei, China.

出版信息

Cancer Cell Int. 2021 Jan 28;21(1):79. doi: 10.1186/s12935-021-01767-5.

DOI:10.1186/s12935-021-01767-5
PMID:33509213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7841906/
Abstract

BACKGROUND

Multiple circular RNAs (circRNAs) have been recently described as crucial oncogenic factors or tumor suppressors. This study aimed to investigate the role of circ_0000020 in glioma progression.

METHODS

Circ_0000020 and miR-142-5p expressions in glioma samples were assessed through qRT-PCR, and then the association between pathological indexes and circ_0000020 expressions was analyzed. Functional experiment was performed with human glioma cell lines U251 and U87. Gain-of-function and loss-of-function models were established. CCK-8 assay was used to detect glioma cell proliferation. Transwell assay was used to examine glioma cell migration and invasion. The regulatory relationships among circ_0000020, miR-142-5p and phosphatidylinositol 3-kinase C (PIK3CA) were investigated by bioinformatics analysis, luciferase reporter assay, qRT-PCR and Western blot. In vivo tumorigenesis assay was performed with nude mice to further validate the demonstrations of in vitro experiments.

RESULTS

Circ_0000020 expression in glioma samples was remarkably increased compared with that in normal brain tissues and its high expression was associated with unfavorable pathological indexes. Circ_0000020 overexpression remarkably accelerated proliferation, migration and invasion of glioma cells. Accordingly, circ_0000020 knockdown suppressed the malignant phenotypes of glioma cells. Circ_0000020 overexpression significantly reduced miR-142-5p expression by sponging it, and circ_0000020 could enhance the expression of PIK3CA, which was a target gene of miR-142-5p.

CONCLUSIONS

Circ_0000020 promotes glioma progression via miR-142-5p/PIK3CA axis.

摘要

背景

最近有研究表明,多种环状RNA(circRNA)是关键的致癌因子或肿瘤抑制因子。本研究旨在探讨circ_0000020在胶质瘤进展中的作用。

方法

通过qRT-PCR评估胶质瘤样本中circ_0000020和miR-142-5p的表达,然后分析病理指标与circ_0000020表达之间的关联。利用人胶质瘤细胞系U251和U87进行功能实验。建立功能获得和功能缺失模型。采用CCK-8法检测胶质瘤细胞增殖。采用Transwell法检测胶质瘤细胞迁移和侵袭能力。通过生物信息学分析、荧光素酶报告基因检测、qRT-PCR和蛋白质免疫印迹法研究circ_0000020、miR-142-5p和磷脂酰肌醇3-激酶C(PIK3CA)之间的调控关系。用裸鼠进行体内成瘤实验,进一步验证体外实验结果。

结果

与正常脑组织相比,胶质瘤样本中circ_0000020表达显著升高,其高表达与不良病理指标相关。circ_0000020过表达显著促进胶质瘤细胞的增殖、迁移和侵袭。相应地,circ_0000020敲低抑制了胶质瘤细胞的恶性表型。circ_0000020过表达通过海绵吸附显著降低miR-142-5p表达,且circ_0000020可增强PIK3CA的表达,PIK3CA是miR-142-5p的靶基因。

结论

circ_000

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/023db8a576cd/12935_2021_1767_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/8c1c4ef5267e/12935_2021_1767_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/bcc16b0d4681/12935_2021_1767_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/b35b6b78aa07/12935_2021_1767_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/023db8a576cd/12935_2021_1767_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/8c1c4ef5267e/12935_2021_1767_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/774d28f7101f/12935_2021_1767_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/4b9754081d90/12935_2021_1767_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/3d59e87d43f9/12935_2021_1767_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/bcc16b0d4681/12935_2021_1767_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/b35b6b78aa07/12935_2021_1767_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d4/7841906/023db8a576cd/12935_2021_1767_Fig7_HTML.jpg

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