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lncRNA OXCT1-AS1 通过稳定 LEF1 促进非小细胞肺癌转移,并且 。

lncRNA OXCT1-AS1 Promotes Metastasis in Non-Small-Cell Lung Cancer by Stabilizing LEF1, and .

机构信息

Department of Thoracic Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, China.

出版信息

Biomed Res Int. 2021 Jul 21;2021:4959381. doi: 10.1155/2021/4959381. eCollection 2021.

Abstract

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the metastasis of non-small-cell lung cancer (NSCLC). This study is aimed at investigating the biological role of lncRNA OXCT1-AS1 in NSCLC metastasis and the underlying regulatory mechanisms. The expression profiles of lncRNA OXCT1-AS1 in different NSCLC cell lines were examined. Then, the biological function of lncRNA OXCT1-AS1 in NSCLC metastasis was explored by loss-of-function assays and . Further, the protective effect of lncRNA OXCT1-AS1 on lymphoid enhancer factor 1 (LEF1) was examined using RNA pull-down and RNA immunoprecipitation assays. Additionally, the role of LEF1 in NSCLC metastasis was investigated. Results indicated that lncRNA OXCT1-AS1 expression was significantly increased in NSCLC cell lines. Functional analysis revealed that knockdown of lncRNA OXCT1-AS1 impaired invasion and migration . Additionally, the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis was also confirmed . Mechanistically, through direct interaction, lncRNA OXCT1-AS1 maintained LEF1 stability by blocking NARF-mediated ubiquitination. Furthermore, LEF1 knockdown impaired invasion and migration of NSCLC and . Collectively, these data highlight the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis by stabilizing LEF1 and suggest that lncRNA OXCT1-AS1 represents a novel therapeutic target in NSCLC.

摘要

长链非编码 RNA(lncRNA)在非小细胞肺癌(NSCLC)转移中发挥着不可忽视的作用。本研究旨在探讨 lncRNA OXCT1-AS1 在 NSCLC 转移中的生物学作用及其潜在的调控机制。检测了不同 NSCLC 细胞系中 lncRNA OXCT1-AS1 的表达谱。然后,通过功能丧失实验探讨了 lncRNA OXCT1-AS1 在 NSCLC 转移中的生物学功能。进一步通过 RNA 下拉和 RNA 免疫沉淀实验检测了 lncRNA OXCT1-AS1 对淋巴增强因子 1(LEF1)的保护作用。此外,还研究了 LEF1 在 NSCLC 转移中的作用。结果表明,lncRNA OXCT1-AS1 在 NSCLC 细胞系中的表达显著增加。功能分析表明,lncRNA OXCT1-AS1 的敲低抑制了侵袭和迁移。此外,还证实了 lncRNA OXCT1-AS1 促进 NSCLC 转移的能力。机制上,通过直接相互作用,lncRNA OXCT1-AS1 通过阻断 NARF 介导的泛素化来维持 LEF1 的稳定性。此外,LEF1 的敲低抑制了 NSCLC 的侵袭和迁移。综上所述,这些数据强调了 lncRNA OXCT1-AS1 通过稳定 LEF1 促进 NSCLC 转移的能力,并表明 lncRNA OXCT1-AS1 是 NSCLC 的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d53/8318766/e705b46ed4b1/BMRI2021-4959381.001.jpg

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