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NCK1-AS1 通过与 MYC 相互作用转录地上调 NCK1 促进肺鳞状细胞癌的进展。

NCK1-AS1 promotes the progression of lung squamous cell carcinoma through transcriptionally upregulating NCK1 via interacting with MYC.

机构信息

Department of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China.

Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.

出版信息

Cancer Biol Ther. 2021 Mar 4;22(3):196-203. doi: 10.1080/15384047.2020.1842717. Epub 2021 Feb 25.

Abstract

Lung squamous cell carcinoma (LUSC) is a prevalent subtype of nonsmall cell lung cancer (NSCLC). Dysregulated long noncoding RNAs (lncRNAs) are increasingly identified as pivotal modulators in cancer progression. NCK1 divergent transcript (NCK1-AS1) is a lncRNA that has been proven to be oncogenic in different types of human cancers. However, whether it exerts similar functions in LUSC remains to be elusive. The present study focused on investigating the influence of NCK1-AS1 on the cellular process in LUSC and exploring its underlying mechanism. Through online bioinformatics analysis, we obtained a high NCK1-AS1 level in LUSC tissues. Meanwhile, we confirmed that NCK1-AS1 was upregulated in LUSC cells. Gain- or loss-of-function assays suggested that NCK1-AS1 prompted cell proliferation and migration, whilst impeded cell apoptosis in LUSC. Mechanistically, we revealed that NCK1-AS1 induced the upregulation of its nearby gene NCK adaptor protein 1 (NCK1) at the transcriptional level by interacting with the transcription factor MYC proto-oncogene (MYC). Rescue assays indicated that NCK1 participated in the regulation of NCK1-AS1 on LUSC progression. In conclusion, we firstly demonstrated the oncogenic role of NCK1-AS1 in LUSC and illustrated its downstream molecular mechanism.

摘要

肺鳞状细胞癌(LUSC)是一种常见的非小细胞肺癌(NSCLC)亚型。失调的长非编码 RNA(lncRNA)被越来越多地认为是癌症进展的关键调节剂。NCK1 发散转录本(NCK1-AS1)是一种 lncRNA,已被证明在不同类型的人类癌症中具有致癌作用。然而,它是否在 LUSC 中发挥类似的功能仍不清楚。本研究重点研究了 NCK1-AS1 对 LUSC 细胞过程的影响,并探讨了其潜在的机制。通过在线生物信息学分析,我们获得了 LUSC 组织中 NCK1-AS1 水平较高的结果。同时,我们证实 NCK1-AS1 在 LUSC 细胞中上调。功能获得或缺失实验表明,NCK1-AS1 促进了 LUSC 细胞的增殖和迁移,同时抑制了细胞凋亡。机制上,我们揭示了 NCK1-AS1 通过与转录因子 MYC 原癌基因(MYC)相互作用,在转录水平上诱导其附近基因 NCK 衔接蛋白 1(NCK1)的上调。挽救实验表明,NCK1 参与了 NCK1-AS1 对 LUSC 进展的调节。总之,我们首次证明了 NCK1-AS1 在 LUSC 中的致癌作用,并阐明了其下游分子机制。

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