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Hsa_circ_0001640通过靶向MiR-942-5p/PTEN轴使PI3K/AKT信号通路失活,从而抑制非小细胞肺癌的进展。

Hsa_circ_0001640 inactivation of the PI3K/AKT signaling pathway by targeting the MiR-942-5p/PTEN axis to inhibit the progression of non-small cell lung cancer.

作者信息

Wang Yanting, Wang Xinlin, Zhang Tao, He Xin

机构信息

Department of Respiratory Medicine, The First Affiliated Hospital of Gannan Medical University, No.23 Qingnian Road, Zhanggong District, Ganzhou, 341000, China; The First Affiliated Hospital of Gannan Medical University, No.23 Qingnian Road, Zhanggong District, Ganzhou, 341000, China.

The First Affiliated Hospital of Gannan Medical University, No.23 Qingnian Road, Zhanggong District, Ganzhou, 341000, China.

出版信息

Exp Cell Res. 2025 Jul 15;450(2):114673. doi: 10.1016/j.yexcr.2025.114673. Epub 2025 Jul 12.

DOI:10.1016/j.yexcr.2025.114673
PMID:40659239
Abstract

Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer with high morbidity and mortality. To identify specific biomarkers, we characterized aberrantly expressed circular RNAs (circRNAs) in NSCLC. We found that hsa_circ_0001640 expression was downregulated in NSCLC tissues and cell lines. Overexpression of hsa_circ_0001640 inhibited proliferation, invasion and migration, and promoted apoptosis in NSCLC cells.Dual-luciferase assays confirmed the interaction between hsa_circ_0001640 and miR-942-5p. Co-transfection of miR-942-5p with hsa_circ_0001640 partially reversed the effects of hsa_circ_0001640 overexpression on tumor cell biological behaviors. Mechanistically, hsa_circ_0001640 inactivated the PI3K/AKT signaling pathway by targeting the miR-942-5p/PTEN axis, thereby suppressing NSCLC progression. Furthermore, in vivo experiments demonstrated that overexpression of hsa_circ_0001640 suppressed the growth of xenograft tumors in mice.Our findings will provide a new marker and possible target for the diagnosis and treatment of NSCLC.

摘要

非小细胞肺癌(NSCLC)是肺癌的主要病理类型,发病率和死亡率都很高。为了鉴定特定的生物标志物,我们对NSCLC中异常表达的环状RNA(circRNA)进行了特征分析。我们发现hsa_circ_0001640在NSCLC组织和细胞系中的表达下调。hsa_circ_0001640的过表达抑制了NSCLC细胞的增殖、侵袭和迁移,并促进了其凋亡。双荧光素酶报告基因检测证实了hsa_circ_0001640与miR-942-5p之间的相互作用。miR-942-5p与hsa_circ_0001640共转染部分逆转了hsa_circ_0001640过表达对肿瘤细胞生物学行为的影响。机制上,hsa_circ_0001640通过靶向miR-942-5p/PTEN轴使PI3K/AKT信号通路失活,从而抑制NSCLC进展。此外,体内实验表明hsa_circ_0001640的过表达抑制了小鼠异种移植瘤的生长。我们的研究结果将为NSCLC的诊断和治疗提供新的标志物和可能的靶点。

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