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长非编码 RNA HCG11 通过与 miR-4425/MTA3 轴合作抑制神经胶质瘤的生长。

Long non-coding RNA HCG11 suppresses the growth of glioma by cooperating with the miR-4425/MTA3 axis.

机构信息

Department of Clinical Laboratory, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.

Department of Neurosurgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China.

出版信息

J Gene Med. 2019 Apr;21(4):e3074. doi: 10.1002/jgm.3074. Epub 2019 Feb 27.

DOI:10.1002/jgm.3074
PMID:30706982
Abstract

BACKGROUND

Glioma is a type of malignant tumor that occurs in the central nervous system of adults. Long non-coding RNAs (lncRNAs) that potentially participate in the initiation and progression of glioma have been widely reported. As a now-found lncRNA, HLA complex group 11 (HCG11) has not yet been studied in glioma. The present study aimed to determine the role of HCG11 in the tumorigenesis of glioma.

METHODS

A quantitative real-time polymerase chain reaction assay was performed to examine the expression pattern of HCG11 in 84 glioma tissues and cell lines. The overall survival rate of glioma patients with a high or low level of HCG11 or metastasis-associated 1 family member 3 (MTA3) was analyzed by Kaplan-Meier analysis. The effect of HCG11 on glioma cell growth was determined by in vitro and in vivo experiments. MicroRNAs (miRNAs) that potentially interact with HCG11 were searched and determined by bioinformatics analysis and a luciferase reporter assay. Similarly, the target of miRNA-4425 was identified. Finally, rescue assays were conducted to determine the bio-function of the competing endogenous RNA pathway.

RESULTS

HCG11 was downregulated in 84 pairs of glioma tissues and cell lines. Moreover, a low level of HCG11 indicted the lower overall survival rate of glioma patients. Regarding the mechanism, HCG11 was abundant in the cytoplasm of glioma cells and interacted with miR-4425 to release the expression of MTA3. miR-4425 and MTA3 participated in HCG11-mediated glioma growth.

CONCLUSIONS

LncRNA HCG11 suppresses the growth of glioma by cooperating with the miR-4425/MTA3 axis.

摘要

背景

神经胶质瘤是一种发生于成人中枢神经系统的恶性肿瘤。大量研究报道长链非编码 RNA(lncRNA)可能参与神经胶质瘤的发生和发展。作为一种新发现的 lncRNA,HLA 复合体 11(HCG11)在神经胶质瘤中的研究尚未见报道。本研究旨在探讨 HCG11 在神经胶质瘤发生发展中的作用。

方法

采用实时荧光定量聚合酶链反应检测 84 例神经胶质瘤组织及细胞系中 HCG11 的表达水平,采用 Kaplan-Meier 分析 HCG11 高表达或低表达以及转移相关基因 1 家族成员 3(MTA3)高表达的神经胶质瘤患者的总生存率。通过体外和体内实验研究 HCG11 对神经胶质瘤细胞生长的影响。采用生物信息学分析和荧光素酶报告基因实验寻找并鉴定与 HCG11 相互作用的 microRNA(miRNA)。同样,确定了 miRNA-4425 的靶基因。最后,通过拯救实验确定竞争性内源 RNA 通路的生物功能。

结果

在 84 对神经胶质瘤组织及细胞系中,HCG11 的表达下调。此外,低水平的 HCG11 预示着神经胶质瘤患者的总生存率较低。就其机制而言,HCG11 在神经胶质瘤细胞的细胞质中含量丰富,并与 miR-4425 相互作用以释放 MTA3 的表达。miR-4425 和 MTA3 参与了 HCG11 介导的神经胶质瘤生长。

结论

lncRNA HCG11 通过与 miR-4425/MTA3 轴相互作用抑制神经胶质瘤的生长。

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