环状 RNA 0004140 通过海绵吸附 miR-330-5p 上调 NOVA2 促进肺腺癌进展。
Circ_0004140 promotes lung adenocarcinoma progression by upregulating NOVA2 via sponging miR-330-5p.
机构信息
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
Department of Respiratory and Critical Care Medicine, The Chengdu Second People's Hospital, Chengdu, China.
出版信息
Thorac Cancer. 2023 Dec;14(35):3483-3494. doi: 10.1111/1759-7714.15141. Epub 2023 Nov 3.
BACKGROUND
Circular RNAs (circRNAs) play a significant role in the tumorigenesis and progression of diverse human cancers, including lung adenocarcinoma. A previous study suggested that circ_0004140 expression was increased in lung adenocarcinoma cells. However, the molecular mechanism of circRNA circ_0004140 involved in lung adenocarcinoma is poorly defined.
METHODS
Circ_0004140, microRNA-330-5p (miR-330-5p), and NOVA alternative splicing regulator 2 (NOVA2) expression were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, invasion, and angiogenesis ability were assessed using 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, transwell, and capillary-like network formation assays. Proliferating cell nuclear antigen (PCNA), cyclin D1, and NOVA2 protein levels were detected using Western blot assay. The interaction between miR-330-5p and circ_0004140 or NOVA2 was verified by dual-luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0004140 in tumor growth in vivo.
RESULTS
Circ_0004140 was upregulated in lung adenocarcinoma tissues and cell lines. Circ_0004140 silencing suppressed cell proliferation, migration, invasion and tube formation ability, and triggered the apoptosis of lung adenocarcinoma cells. Circ_0004140 acted as a molecular sponge for miR-330-5p, and miR-330-5p silencing largely reversed circ_0004140 knockdown-induced effects in lung adenocarcinoma cells. NOVA2 was a target of miR-330-5p, and NOVA2 overexpression might largely overturn miR-330-5p overexpression-induced influences in lung adenocarcinoma cells. Circ_0004140 upregulated NOVA2 expression via sponging miR-330-5p in lung adenocarcinoma cells. Circ_0004140 silencing restrained xenograft tumor growth in vivo.
CONCLUSION
Circ_0004140 knockdown might suppress the malignant biological behaviors of lung adenocarcinoma cells via miR-330-5p-dependent regulation of NOVA2.
背景
环状 RNA（circRNAs）在多种人类癌症的肿瘤发生和进展中发挥重要作用，包括肺腺癌。先前的研究表明，circ_0004140 在肺腺癌细胞中的表达增加。然而，circRNA circ_0004140 参与肺腺癌的分子机制尚不清楚。
方法
通过实时定量聚合酶链反应（RT-qPCR）测定 circ_0004140、microRNA-330-5p（miR-330-5p）和 NOV A 剪接调节因子 2（NOVA2）的表达。使用 5-乙炔基-2'-脱氧尿苷（EdU）、流式细胞术、划痕愈合、Transwell 和毛细血管样网络形成测定评估细胞增殖、凋亡、迁移、侵袭和血管生成能力。使用 Western blot 检测增殖细胞核抗原（PCNA）、细胞周期蛋白 D1 和 NOVA2 蛋白水平。通过双荧光素酶报告基因检测验证 miR-330-5p 与 circ_0004140 或 NOVA2 之间的相互作用。利用异种移植肿瘤模型评估 circ_0004140 在体内肿瘤生长中的作用。
结果
circ_0004140 在肺腺癌组织和细胞系中上调。circ_0004140 沉默抑制肺腺癌细胞的增殖、迁移、侵袭和管形成能力，并触发肺腺癌细胞凋亡。circ_0004140 作为 miR-330-5p 的分子海绵，而 miR-330-5p 沉默在很大程度上逆转了肺腺癌细胞中 circ_0004140 敲低诱导的效应。NOVA2 是 miR-330-5p 的靶基因，而 miR-330-5p 过表达在很大程度上推翻了肺腺癌细胞中 miR-330-5p 过表达诱导的影响。circ_0004140 通过在肺腺癌细胞中海绵吸附 miR-330-5p 而上调 NOVA2 表达。circ_0004140 沉默抑制体内异种移植肿瘤生长。
结论
circ_0004140 敲低可能通过 miR-330-5p 依赖性调节 NOV A2 抑制肺腺癌细胞的恶性生物学行为。
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