Department of Neurosurgery, Linyi Central Hospital , Linyi, Shandong, P.R. China.
Department of Neurology, The Second People's Hospital of Liaocheng Affiliated to Shandong First Medical University , Liaocheng, Shandong, P.R. China.
Neurol Res. 2021 Mar;43(3):210-219. doi: 10.1080/01616412.2020.1836465. Epub 2020 Oct 18.
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.
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.
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.
LIFR-AS1 could suppress the proliferation, migration and invasion and promote the apoptosis through modulating miR-4262/NF-κB pathway in glioma.
本研究旨在探讨长链非编码 RNA 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的分子机制。
采用实时定量聚合酶链反应（qRT-PCR）检测胶质瘤组织和细胞系中 LIFR-AS1 和 miR-4262 的表达。采用集落形成实验、5-乙炔基-20-脱氧尿苷（EdU）实验、流式细胞术和 Transwell 实验分别检测细胞克隆、增殖、凋亡、迁移和侵袭。还分析了 LIFR-AS1 对胶质瘤细胞对替莫唑胺（TMZ）化疗耐药性的影响。此外，还进行了双荧光素酶报告基因实验来评估荧光素酶活性。通过 Western blot 检测胶质瘤细胞中核因子-κB（NF-κB）p65、磷酸化 NF-κB p65（p-NF-κB p65）和κB 抑制蛋白α（IκBα）的表达。
LIFR-AS1 在胶质瘤组织和细胞系中低表达，miR-4262 高表达。LIFR-AS1 过表达抑制了胶质瘤细胞的增殖、迁移和侵袭，并促进了细胞凋亡。LIFR-AS1 过表达还降低了胶质瘤细胞对 TMZ 的化疗耐药性。此外，LIFR-AS1 过表达抑制了胶质瘤细胞中 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 阻断了 LIFR-AS1 在 NF-κB 通路中对胶质瘤细胞增殖、凋亡、迁移和侵袭的作用。
LIFR-AS1 可通过调节 miR-4262/NF-κB 通路抑制胶质瘤细胞的增殖、迁移和侵袭，促进细胞凋亡。
