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

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-09-28 DOI:10.1186/s12943-024-02120-w

Meina Jiang, Huihui Bai, Shuai Fang, Chengwei Zhou, Weiyu Shen, Zhaohui Gong

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引用次数: 0

Abstract

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. 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. 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. 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.

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CircLIFRSA/miR-1305/PTEN轴通过调节AKT磷酸化减轻非小细胞肺癌的恶性细胞过程

非小细胞肺癌（NSCLC）通常在晚期才被诊断出来，这限制了治疗干预措施的有效性。本研究旨在探讨新发现的circLIFRSA在PTEN/AKT信号通路中的作用及其在NSCLC恶性过程中的参与。通过芯片分析确定了circLIFRSA的表达，并通过RT-qPCR对其在NSCLC样本中的水平进行了量化。通过 MTT 试验、集落形成试验和流式细胞术评估了 circLIFRSA 对细胞生长、增殖、凋亡和细胞周期的影响。此外，还采用 Western 印迹法分析了 NSCLC 细胞中 PTEN 和磷酸化 AKT（pAKT）的表达。研究发现，circLIFRSA在NSCLC细胞和组织中的表达明显降低。这种表达下调与各种临床病理特征相关，表明其具有作为 NSCLC 早期诊断生物标记物的潜力。重要的是，研究表明 circLIFRSA 可抑制细胞生长和增殖，同时促进 NSCLC 细胞凋亡。研究发现，circLIFRSA通过miR-1305/PTEN轴和AKT磷酸化抑制作用，从机制上减轻了NSCLC细胞的恶性过程。这些研究结果表明，circLIFRSA/miR-1305/PTEN轴通过调节AKT磷酸化来减弱恶性过程，并为circLIFRSA作为早期诊断生物标志物和NSCLC治疗靶点的潜力提供了新的见解。

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

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.