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长链非编码 RNA DDX11-AS1 通过调节 PI3K/AKT 信号通路促进非小细胞肺癌的发展。

Long non-coding RNA DDX11-AS1 promotes non-small cell lung cancer development via regulating PI3K/AKT signalling.

机构信息

Department of Cardiothoracic Surgery, 900th Hospital of Joint Logistics Support Force of People's Liberation Army, Fuzhou, China.

出版信息

Clin Exp Pharmacol Physiol. 2020 Sep;47(9):1622-1631. doi: 10.1111/1440-1681.13325. Epub 2020 May 13.

DOI:10.1111/1440-1681.13325
PMID:32298476
Abstract

Non-small cell lung cancer (NSCLC) has been considered to be the most common category of lung cancer, comprising approximately 80% of lung cancers. Long non-coding RNAs (lncRNAs) were diffusely documented to modulate carcinogenesis or progression of tumours. However, the role of DDX11-AS1 was still unclear in NSCLC. Bioinformatics analysis and experimental assays including hematoxylin and eosin (H&E) staining, RT-qPCR, colony formation, CCK-8, flow cytometry, western blot and xenograft assays were applied to investigate the biological role and molecular mechanism of DDX11-AS1 in NSCLC. The level of lncRNA DDX11-AS1 was up-regulated in NSCLC tumour tissues and cells. In function aspect, knockdown of DDX11-AS1 caused an apparent inhibitive effect on cell proliferation in vitro and in vivo. DDX11-AS1 inhibition promoted cell apoptosis in vitro. In mechanism, the protein level of phosphorylated AKT was reduced by DDX11-AS1 inhibition but increased by DDX11-AS1 overexpression. These results indicated that DDX11-AS1 exacerbated NSCLC progression via activating PI3K/AKT signalling pathway. All in all, DDX11-AS1 promotes NSCLC development via regulating PI3K/AKT signalling.

摘要

非小细胞肺癌(NSCLC)被认为是最常见的肺癌类型,约占肺癌的 80%。长链非编码 RNA(lncRNA)被广泛证明可调节肿瘤的发生或进展。然而,DDX11-AS1 在 NSCLC 中的作用仍不清楚。生物信息学分析和实验检测,包括苏木精和伊红(H&E)染色、RT-qPCR、集落形成、CCK-8、流式细胞术、Western blot 和异种移植实验,用于研究 DDX11-AS1 在 NSCLC 中的生物学作用和分子机制。lncRNA DDX11-AS1 在 NSCLC 肿瘤组织和细胞中呈上调表达。在功能方面,DDX11-AS1 的敲低显著抑制了体外和体内的细胞增殖。DDX11-AS1 抑制促进了体外细胞凋亡。在机制上,DDX11-AS1 抑制降低了磷酸化 AKT 的蛋白水平,但通过 DDX11-AS1 过表达增加了磷酸化 AKT 的蛋白水平。这些结果表明,DDX11-AS1 通过激活 PI3K/AKT 信号通路加剧 NSCLC 进展。总之,DDX11-AS1 通过调节 PI3K/AKT 信号通路促进 NSCLC 的发展。

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