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.

中文翻译：

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CircLIFRSA/miR-1305/PTEN 轴通过调节 AKT 磷酸化来减弱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。通过微阵列分析鉴定 CircLIFRSA 表达，并通过 RT-qPCR 定量 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，采用蛋白质印迹法分析 NSCLC 细胞中 PTEN 和磷酸化 AKT (pAKT) 的表达。发现 circLIFRSA 的表达在 NSCLC 细胞和组织中显着降低。这种下调与各种临床病理学特征相关，表明其作为 NSCLC 早期诊断生物标志物的潜力。重要的是，circLIFRSA 被证明可以抑制细胞生长和增殖，同时促进 NSCLC 细胞凋亡。从机械角度来看，circLIFRSA 可通过 miR-1305/PTEN 轴和抑制 AKT 磷酸化来减弱 NSCLC 细胞的恶性过程。这些发现表明，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作为 NSCLC 有前景的治疗靶点的潜力提供了新的见解。