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环状 LIFRSA/miR-1305/PTEN 轴通过调节 AKT 磷酸化抑制非小细胞肺癌中的恶性细胞过程。

CircLIFRSA/miR-1305/PTEN axis attenuates malignant cellular processes in non-small cell lung cancer by regulating AKT phosphorylation.

机构信息

Department of Biochemistry and Molecular Biology and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China.

Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China.

出版信息

Mol Cancer. 2024 Sep 28;23(1):208. doi: 10.1186/s12943-024-02120-w.

Abstract

BACKGROUND

Non-small cell lung cancer (NSCLC) is typically diagnosed at advanced stages, which limits the effectiveness of therapeutic interventions. The present study aimed to explore the role of the newly identified circLIFRSA in the PTEN/AKT signaling pathway and its involvement in the malignant processes of NSCLC.

METHODS

CircLIFRSA expression was identified through microarray analysis, and its levels in NSCLC samples were quantified by RT-qPCR. The impact of circLIFRSA on cell growth, proliferation, apoptosis, and cell cycle were evaluated by MTT assay, colony formation assay, and flow cytometry. Additionally, Western blotting was employed to analyze the expression of PTEN and phosphorylated AKT (pAKT) in NSCLC cells.

RESULTS

The expression of circLIFRSA was found to be significantly reduced in NSCLC cells and tissues. This downregulation correlated with various clinicopathological characteristics and indicated its potential as an early diagnostic biomarker for NSCLC. Importantly, circLIFRSA was shown to inhibit cell growth and proliferation while promoting apoptosis in NSCLC cells. Mechanically, circLIFRSA was found to attenuate the malignant processes of NSCLC cells via the miR-1305/PTEN axis and the suppression of AKT phosphorylation.

CONCLUSIONS

These findings indicate that circLIFRSA/miR-1305/PTEN axis attenuates malignant processes by regulating AKT phosphorylation, and provide new insights into the potential of circLIFRSA as a biomarker for early diagnosis and as a promising therapeutic target in NSCLC.

摘要

背景

非小细胞肺癌(NSCLC)通常在晚期诊断,这限制了治疗干预的效果。本研究旨在探讨新鉴定的环状 LIFRSA 在 PTEN/AKT 信号通路中的作用及其在 NSCLC 恶性进程中的参与。

方法

通过微阵列分析鉴定 circLIFRSA 的表达,并通过 RT-qPCR 定量检测 NSCLC 样本中的水平。通过 MTT 测定、集落形成测定和流式细胞术评估 circLIFRSA 对细胞生长、增殖、凋亡和细胞周期的影响。此外,还采用 Western blot 分析 NSCLC 细胞中 PTEN 和磷酸化 AKT(pAKT)的表达。

结果

发现 circLIFRSA 在 NSCLC 细胞和组织中的表达显著降低。这种下调与各种临床病理特征相关,并表明其作为 NSCLC 早期诊断生物标志物的潜力。重要的是,circLIFRSA 被证明可抑制 NSCLC 细胞的生长和增殖,同时促进细胞凋亡。机制上,circLIFRSA 通过 miR-1305/PTEN 轴和抑制 AKT 磷酸化来抑制 NSCLC 细胞的恶性进程。

结论

这些发现表明 circLIFRSA/miR-1305/PTEN 轴通过调节 AKT 磷酸化来减弱恶性进程,并为 circLIFRSA 作为早期诊断生物标志物和 NSCLC 有前途的治疗靶点提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/853c/11438201/0bff17c88915/12943_2024_2120_Fig2_HTML.jpg

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