Lung adenocarcinoma (LUAD) is a common subtype of lung cancer with high recurrence rate and fatality. Circ_0001361 has been recognized as key regulators in various malignancies, but its roles in LUAD remain ambiguous. Circ_0001361, miR-525-5p, and VMA21 levels were assessed by RT-qPCR. The growth and metastasis of LUAD cells were detected by MTT, colony formation, wound scratch, and transwell assays, respectively. The interaction between circ_0001361/VMA21 and miR-525-5p was detected by dual luciferase, RNA immunoprecipitation, and RNA pull-down assays. VMA21 protein level was detected by Western blotting. Nude mouse xenograft model was established to determine the role of circ_0001361 in tumor growth in vivo. Circ_0001361 was up-regulated, while miR-525-5p was down-regulated in LUAD tissues and cells. Functional experiments demonstrated that circ_0001361 drove LUAD cell growth and metastasis. Mechanistically, circ_0001361 functioned as a sponge of miR-525-5p to up-regulate downstream target VMA21 level. MiR-525-5p/VMA21 axis was involved in circ_0001361-mediated malignant phenotypes of LUAD cells. Finally, inhibition of circ_0001361 restrained in vivo xenograft tumor growth via regulating miR-525-5p/VMA21 axis. Our findings elucidate that circ_0001361 facilitates the tumorigenesis and development of LUAD through miR-525-5p/VMA21 axis, providing evidence for circ_0001361 as a potential prognosis biomarker and therapeutic target for clinical treatment of LUAD.

中文翻译：

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Hsa_circ_0001361通过靶向miR-525-5p/VMA21轴促进肺腺癌细胞的进展

肺腺癌（LUAD）是一种常见的肺癌亚型，具有较高的复发率和致死率。Circ_0001361 已被公认为各种恶性肿瘤的关键调节剂，但其在 LUAD 中的作用仍然模棱两可。通过 RT-qPCR 评估 Circ_0001361、miR-525-5p 和 VMA21 水平。分别通过MTT、集落形成、伤口划痕和transwell测定法检测LUAD细胞的生长和转移。circ_0001361/VMA21 和 miR-525-5p 之间的相互作用通过双荧光素酶、RNA 免疫沉淀和 RNA 下拉试验检测。通过Western印迹检测VMA21蛋白水平。建立裸鼠异种移植模型以确定circ_0001361在体内肿瘤生长中的作用。Circ_0001361 上调，而 miR-525-5p 在 LUAD 组织和细胞中下调。功能实验表明，circ_0001361 驱动了 LUAD 细胞的生长和转移。机制上，circ_0001361 充当 miR-525-5p 的海绵，以上调下游目标 VMA21 水平。MiR-525-5p/VMA21 轴参与 circ_0001361 介导的 LUAD 细胞恶性表型。最后，抑制 circ_0001361 通过调节 miR-525-5p/VMA21 轴来抑制体内异种移植肿瘤的生长。我们的研究结果阐明了circ_0001361通过miR-525-5p/VMA21轴促进了LUAD的肿瘤发生和发展，为circ_0001361作为临床治疗LUAD的潜在预后生物标志物和治疗靶点提供了证据。MiR-525-5p/VMA21 轴参与 circ_0001361 介导的 LUAD 细胞恶性表型。最后，抑制 circ_0001361 通过调节 miR-525-5p/VMA21 轴来抑制体内异种移植肿瘤的生长。我们的研究结果阐明了circ_0001361通过miR-525-5p/VMA21轴促进了LUAD的肿瘤发生和发展，为circ_0001361作为临床治疗LUAD的潜在预后生物标志物和治疗靶点提供了证据。MiR-525-5p/VMA21 轴参与 circ_0001361 介导的 LUAD 细胞恶性表型。最后，抑制 circ_0001361 通过调节 miR-525-5p/VMA21 轴来抑制体内异种移植肿瘤的生长。我们的研究结果阐明了circ_0001361通过miR-525-5p/VMA21轴促进了LUAD的肿瘤发生和发展，为circ_0001361作为临床治疗LUAD的潜在预后生物标志物和治疗靶点提供了证据。