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环状 RNA circFOXK2 通过 miR-149-3p/IL-6 轴促进非小细胞肺癌的肿瘤发生。

The Circular RNA circFOXK2 Enhances the Tumorigenesis of Non-Small Cell Lung Cancer Through the miR-149-3p/IL-6 Axis.

机构信息

Department of Respiratory and Critical Care Medicine, Yinzhou People's Hospital, The Affiliated People's Hospital of Ningbo University, Ningbo, 315000, China.

Department of Central Laboratory, Yinzhou People's Hospital, The Affiliated People's Hospital of Ningbo University, Ningbo, 315000, China.

出版信息

Biochem Genet. 2024 Feb;62(1):95-111. doi: 10.1007/s10528-023-10394-w. Epub 2023 May 31.

DOI:10.1007/s10528-023-10394-w
PMID:37256441
Abstract

Circular RNAs (circRNAs) are the non-coding types of RNAs and are thoughts to be linked with human cancer progression. circFOXK2 is believed to be associated with cancers, however, the molecular mechanisms of circFOXK2 in non-small cell lung cancer (NSCLC) are still unclear. Here we firstly reported that circFOXK2 enhances the tumorigenesis of NSCLC through the miR-149-3p/IL-6 axis. The expression of circFOXK2, microRNA-149-3p (miR-149-3p) and IL-6 were assessed by qRT-PCR and western blot. Transwell, colony formation, wound healing, and CCK-8 assays were used to elucidate NSCLC cells' proliferation, migration, and invasion. MiR-149-3p interaction with circFOXK2 was confirmed by dual-luciferase reporter gene assay (DLRGA). Furthermore, the biological effect of circFOXK2 on NSCLC progression was detected by tumor xenograft assay. CircFOXK2 were upregulated in NSCLC tissues and cells, miR-149-3p were downregulated in NSCLC tissues and cells. In addition, circFOXK2 stimulated NSCLC cell proliferation, migration and invasion in vitro. Mechanical analysis indicated that circFOXK2 modulated IL-6 via miR-149-3p sponging. Furthermore, circFOXK2 overexpression promoted tumor growth in vivo. Overall, this research verified that circFOXK2 enhances the tumorigenesis of NSCLC through the miR-149-3p/IL-6 axis.

摘要

环形 RNA(circRNAs)是非编码 RNA 类型,被认为与人类癌症进展有关。circFOXK2 被认为与癌症有关,然而,circFOXK2 在非小细胞肺癌(NSCLC)中的分子机制尚不清楚。在这里,我们首次报道 circFOXK2 通过 miR-149-3p/IL-6 轴增强 NSCLC 的肿瘤发生。通过 qRT-PCR 和 Western blot 评估 circFOXK2、微小 RNA-149-3p(miR-149-3p)和 IL-6 的表达。Transwell、集落形成、划痕愈合和 CCK-8 测定用于阐明 NSCLC 细胞的增殖、迁移和侵袭。通过双荧光素酶报告基因测定(DLRGA)证实了 miR-149-3p 与 circFOXK2 的相互作用。此外,通过肿瘤异种移植实验检测 circFOXK2 对 NSCLC 进展的生物学影响。circFOXK2 在 NSCLC 组织和细胞中上调,miR-149-3p 在 NSCLC 组织和细胞中下调。此外,circFOXK2 在体外刺激 NSCLC 细胞增殖、迁移和侵袭。力学分析表明,circFOXK2 通过 miR-149-3p 海绵作用调节 IL-6。此外,circFOXK2 的过表达促进了体内肿瘤的生长。总的来说,这项研究验证了 circFOXK2 通过 miR-149-3p/IL-6 轴增强 NSCLC 的肿瘤发生。

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