肺腺癌(LUAD)是肺癌的常见亚型,复发率高,病死率高。Circ_0001361已被公认为各种恶性肿瘤的关键监管机构,但它在LUAD中的作用仍然模棱两可。
Circ_0001361,miR-525-5p,通过RT-qPCR评估VMA21水平。MTT法检测LUAD细胞的生长和转移,菌落形成,伤口划伤,和transwell分析,分别。双荧光素酶检测circ_0001361/VMA21与miR-525-5p的相互作用,RNA免疫沉淀,和RNA下拉法。通过蛋白质印迹法检测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LUAD细胞生长和转移。机械上,circ_0001361充当miR-525-5p的海绵以上调下游靶VMA21水平。MiR-525-5p/VMA21轴参与LUAD细胞的circ_0001361介导的恶性表型。最后,抑制circ_0001361通过调节miR-525-5p/VMA21轴抑制体内异种移植瘤的生长。
我们的发现阐明circ_0001361通过miR-525-5p/VMA21轴促进LUAD的肿瘤发生和发展,为circ_0001361作为LUAD临床治疗的潜在预后生物标志物和治疗靶点提供证据。
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.