RNF144A-AS1 通过靶向 miR-665/HMGA1 轴促进神经胶质瘤细胞的发展。

RNF144A-AS1 promotes the development of glioma cells by targeting miR-665/HMGA1 axis.

机构信息

Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, China.

出版信息

Neurosci Lett. 2021 Nov 20;765:136259. doi: 10.1016/j.neulet.2021.136259. Epub 2021 Sep 22.

DOI:10.1016/j.neulet.2021.136259

PMID:34560189

Abstract

PURPOSE

Glioma is a malignant tumor in the central nervous system. Long non-coding RNA (lncRNA) RNF144A-AS1 exerts a regulatory effect in cancers, but its role in glioma remains obscure and needs to be further study.

METHODS

Expressions of RNF144A-AS1, miR-665 and High-mobility group A1 (HMGA1) in glioma tissues and/or cells were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The relationship between miR-665 and RNF144A-AS1/HMGA1 was determined by bioinformatics and Dual-Luciferase Reporter assay. The effect of RNF144A-AS1 on the biological functions of glioma cells was confirmed by loss and gain experiments (including cell counting kit 8, clone formation, wound healing, Transwell, qRT-PCR and western blot). The regulatory mechanism of RNF144A-AS1/miR-665/HMGA1 axis on glioma was confirmed by rescue experiments.

RESULTS

RNF144A-AS1 and HMGA1 were high-expressed in gliomas, and miR-665 was low-expressed in gliomas, which led to the increase of glioma cell viability, proliferation, migration and invasion ability and insufficient apoptosis ability. Overexpression of RNF144A-AS1 suppressed the expressions of Bax and cleaved caspase-3, and promoted Bcl-2 expression. RNF144A-AS1 up-regulated the expression of HMGA1 by targeting miR-665, thereby promoting the development of glioma cells.

CONCLUSION

RNF144A-AS1/miR-665/HMGA1 axis implicated in the development of glioma.

摘要

目的

神经胶质瘤是一种中枢神经系统的恶性肿瘤。长链非编码 RNA（lncRNA）RNF144A-AS1 在癌症中发挥调节作用，但它在神经胶质瘤中的作用尚不清楚，需要进一步研究。

方法

通过实时定量逆转录聚合酶链反应（qRT-PCR）测定神经胶质瘤组织和/或细胞中 RNF144A-AS1、miR-665 和高迁移率族蛋白 A1（HMGA1）的表达。通过生物信息学和双荧光素酶报告基因检测确定 miR-665 与 RNF144A-AS1/HMGA1 的关系。通过缺失和获得实验（包括细胞计数试剂盒 8、克隆形成、划痕愈合、Transwell、qRT-PCR 和 Western blot）证实 RNF144A-AS1 对神经胶质瘤细胞生物学功能的影响。通过挽救实验证实 RNF144A-AS1/miR-665/HMGA1 轴对神经胶质瘤的调控机制。

结果

RNF144A-AS1 和 HMGA1 在神经胶质瘤中高表达，miR-665 在神经胶质瘤中低表达，导致神经胶质瘤细胞活力、增殖、迁移和侵袭能力增加，凋亡能力不足。RNF144A-AS1 的过表达抑制 Bax 和 cleaved caspase-3 的表达，促进 Bcl-2 的表达。RNF144A-AS1 通过靶向 miR-665 上调 HMGA1 的表达，从而促进神经胶质瘤细胞的发展。