ABSTRACT

Aim

This study aimed to explore the role of lncRNA leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) on glioma and its underlying molecular mechanism.

Methods

The expression of LIFR-AS1 and miR-4262 was detected by quantitative real-time polymerase chain reaction (qRT-RCR) in both glioma tissues and cell lines. Colony formation assay, 5-ethynyl-20-deoxyuridine (EdU) assay, flow cytometry and transwell assay were respectively conducted to detect cell clones, proliferation, apoptosis, migration and invasion. The effect of LIFR-AS1 on the chemoresistance to temozolomide (TMZ) of glioma cells was also analyzed. In addition, dual-luciferase reporter gene assay was performed to evaluate the luciferase activity. The expressions of nuclear factor-κB (NF-κB) p65, p-NF-κB p65 and inhibitor of κBα (IκBα) in glioma cells were measured by western blot.

Results

LIFR-AS1 was lowly expressed and miR-4262 was highly expressed in glioma tissues and cell lines. LIFR-AS1 overexpression inhibited the proliferation, migration and invasion and promoted apoptosis of glioma cells. LIFR-AS1 overexpression also reduced the chemoresistance to TMZ of glioma cells. Moreover, LIFR-AS1 overexpression suppressed the activation of NF-κB signaling pathway in glioma cells. miR-4262 was the target gene of LIFR-AS1. We also found that miR-4262 abrogated the functions of LIFR-AS1 on cell proliferation, apoptosis, migration and invasion of glioma cells in the NF-κB pathway.

Conclusion

LIFR-AS1 could suppress the proliferation, migration and invasion and promote the apoptosis through modulating miR-4262/NF-κB pathway in glioma.

中文翻译：

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长链非编码RNA LIFR-AS1通过调节胶质瘤中的miR-4262/NF-κB通路抑制增殖、迁移和侵袭并促进细胞凋亡

摘要

目的

本研究旨在探讨lncRNA白血病抑制因子受体反义RNA 1（LIFR-AS1）在胶质瘤中的作用及其潜在分子机制。

方法

通过定量实时聚合酶链反应 (qRT-RCR) 在胶质瘤组织和细胞系中检测 LIFR-AS1 和 miR-4262 的表达。分别进行集落形成试验、5-乙炔基-20-脱氧尿苷(EdU)试验、流式细胞术和transwell试验检测细胞克隆、增殖、凋亡、迁移和侵袭。还分析了 LIFR-AS1 对神经胶质瘤细胞对替莫唑胺 (TMZ) 化学抗性的影响。此外，还进行了双荧光素酶报告基因测定以评估荧光素酶活性。Western blot检测神经胶质瘤细胞核因子-κB（NF-κB）p65、p-NF-κB p65和κBα抑制剂（IκBα）的表达。

结果

LIFR-AS1在神经胶质瘤组织和细胞系中低表达而miR-4262高表达。LIFR-AS1过表达抑制胶质瘤细胞的增殖、迁移和侵袭，促进其凋亡。LIFR-AS1 过表达也降低了胶质瘤细胞对 TMZ 的化学抗性。此外，LIFR-AS1 过表达抑制了神经胶质瘤细胞中 NF-κB 信号通路的激活。miR-4262 是 LIFR-AS1 的靶基因。我们还发现miR-4262在NF-κB通路中废除了LIFR-AS1对神经胶质瘤细胞增殖、凋亡、迁移和侵袭的功能。

结论

LIFR-AS1可通过调节miR-4262/NF-κB通路抑制胶质瘤的增殖、迁移和侵袭，促进细胞凋亡。