N6-methyladenosine-modified circ_0000517 promotes non-small cell lung cancer metastasis via miR-1233-3p/CDH6 axis

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2025-04-25 DOI:10.1007/s10735-025-10421-7

Weixian Lin, Lifang Huang, Zhu’an Ou, Yiwen Xuan, Daoqi Zhu, Qipeng Zhang, Enwu Xu

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引用次数: 0

Abstract

Circular RNAs (circRNAs) exhibit dysregulation in non-small cell lung cancer (NSCLC) and regulate the malignant biological behavior of NSCLC. The N6-methyladenosine (m6A) modification of circRNAs plays a critical role in multiple malignant tumors, and their biological relevance in NSCLC is unclear. Herein, this study was conducted to investigate the novel functional mechanism of highly expressed circ_0000517 in NSCLC by developing in vitro experiments. We found that circ_0000517 was upregulated in NSCLC tissues and cells, and that increased circ_0000517 expression was associated with m6A modification. Biologically, silenced circ_0000517 hindered the proliferation, colony formation, migration and invasion of NSCLC cells in vitro, and also suppressed the EMT-related process. Mechanistically, highly expressed circ_0000517 activated CDH6 expression and EMT evolution through sponging miR-1233-3p. Notably, miR-1233-3p had the opposite effect and reversed the promotion effect of circ_0000517 on the malignant biological behavior of NSCLC cells. Our study revealed a promising novel endogenous regulatory network that m6A-modified circ_0000517 accelerated malignant evolution of NSCLC by targeting the miR-1233-3p/CDH6 axis.

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n6 -甲基腺苷修饰的circ_0000517通过miR-1233-3p/CDH6轴促进非小细胞肺癌转移

环状 RNA（circRNA）在非小细胞肺癌（NSCLC）中表现出失调，并调控 NSCLC 的恶性生物学行为。circRNAs的N6-甲基腺苷（m6A）修饰在多种恶性肿瘤中起着关键作用，而它们在NSCLC中的生物学相关性尚不清楚。本研究通过体外实验研究了高表达的circ_0000517在NSCLC中的新功能机制。我们发现，circ_0000517在NSCLC组织和细胞中上调，并且circ_0000517表达的增加与m6A修饰有关。在生物学上，沉默的circ_0000517阻碍了体外NSCLC细胞的增殖、集落形成、迁移和侵袭，也抑制了EMT相关过程。从机理上讲，高表达的circ_0000517通过海绵化miR-1233-3p激活了CDH6的表达和EMT的演化。值得注意的是，miR-1233-3p具有相反的作用，它逆转了circ_0000517对NSCLC细胞恶性生物学行为的促进作用。我们的研究揭示了一个很有前景的新型内源性调控网络，即m6A修饰的circ_0000517通过靶向miR-1233-3p/CDH6轴加速了NSCLC的恶性演化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.