长链非编码 RNA NORAD 通过靶向 miR-451 促进甲状腺癌进展。
LncRNA NORAD promotes thyroid carcinoma progression by targeting miR-451.
机构信息
Department of Nuclear Medicine, Weihai Central Hospital, Weihai, China.
出版信息
Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6187-6195. doi: 10.26355/eurrev_202110_26989.
OBJECTIVE
Long non-coding RNA (lncRNA) NORAD plays an essential role in the development and progress of papillary thyroid carcinoma (PTC). MicroRNA-451 (MiR-451) has been identified as playing an inhibitory role in some types of cancer. However, the molecular mechanism of lncRNA NORAD regulating metastasis of PTC cells by miR-451 has not been fully elucidated.
MATERIALS AND METHODS
Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) or Western blot analysis of the expression of NORAD, miR-451, and interleukin-6 receptor (IL-6R) in PTC cell lines were carried out. The detection of Luciferase reporter gene showed the relationship between lncRNA NORAD, miR-451 and IL-6R. Cell Counting Kit-8 (CCK-8) assay and transwell assay were performed to detect the influence of lncRNA NORAD, miR-451 on the proliferation, migration, and invasion of PTC cells.
RESULTS
The results of RT-qPCR and Western blotting suggested that the expression of lncRNA NORAD and IL-6R were higher than that of the control group, while the expression of miR-451 was lower. Transwell assay indicated that the knockdown of lncRNA NORAD or overexpression of miR-451 significantly inhibited cell proliferation, migration and invasion in PTC cell lines. In addition, lncRNA NORAD negatively controls the expression of miR-451, resulting in the upregulation of IL-6R. IL-6R overexpression can reverse the inhibitory effect of lncRNA NORAD knockdown or miR-451 on PTC cell proliferation and metastasis.
CONCLUSIONS
Our results indicated that the cell migration and invasion were inhibited by knockdown of lncRNA NORAD or overexpression of miR-451, suggesting that the axis of lncRNA NORAD -miR-451- IL-6R was involved in the development of PTC.
目的
长链非编码 RNA（lncRNA）NORAD 在甲状腺乳头状癌（PTC）的发生发展中发挥着重要作用。miR-451 已被确定在某些类型的癌症中发挥抑制作用。然而，lncRNA NORAD 通过 miR-451 调节 PTC 细胞转移的分子机制尚未完全阐明。
材料和方法
采用实时定量聚合酶链反应（RT-qPCR）或 Western blot 分析 PTC 细胞系中 NORAD、miR-451 和白细胞介素 6 受体（IL-6R）的表达。通过荧光素酶报告基因检测，研究 lncRNA NORAD、miR-451 和 IL-6R 之间的关系。细胞计数试剂盒-8（CCK-8）检测和 Transwell 检测用于检测 lncRNA NORAD、miR-451 对 PTC 细胞增殖、迁移和侵袭的影响。
结果
RT-qPCR 和 Western blot 结果表明，lncRNA NORAD 和 IL-6R 的表达高于对照组，而 miR-451 的表达则较低。Transwell 实验表明，lncRNA NORAD 敲低或 miR-451 过表达可显著抑制 PTC 细胞系的增殖、迁移和侵袭。此外，lncRNA NORAD 负调控 miR-451 的表达，导致 IL-6R 上调。IL-6R 过表达可逆转 lncRNA NORAD 敲低或 miR-451 对 PTC 细胞增殖和转移的抑制作用。
结论
我们的研究结果表明，lncRNA NORAD 敲低或 miR-451 过表达抑制了细胞迁移和侵袭，提示 lncRNA NORAD-miR-451-IL-6R 轴参与了 PTC 的发生发展。
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