Department of Respiratory Medicine, Zhejiang Jinhua Guangfu Cancer Hospital, Jinhua, China.
Thorac Cancer. 2023 Dec;14(35):3453-3464. doi: 10.1111/1759-7714.15138. Epub 2023 Oct 20.
Circular RNAs (circRNAs) are involved in the malignant development of tumors. However, the mechanism of circ_0102231 in non-small cell lung cancer (NSCLC) has rarely been discussed and reported.
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of circ_0102231, miR-635 and NOVA alternative splicing regulator 2 (NOVA2) in NSCLC tissues and cells. Western blot was applied to detect the protein expression. Cell proliferation was monitored by cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) experiments. The angiogenesis ability of cells was tested by angiogenesis assay. Flow cytometry was used to analyze cell apoptosis. The relationship between circ_0102231 and NOVA2 or miR-635 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. An in vivo transplanted tumor model was established to confirm the effect of circ_0102231 on tumor formation.
Circ_0102231 was abnormally upregulated in NSCLC tissues and correlated with clinical stage. Silencing of circ_0102231 inhibited cell proliferation and angiogenesis but significantly promoted the apoptosis of NSCLC cells. There were target binding sites between circ_0102231 and miR-635, miR-635 and NOVA2. Importantly, circ_0102231 acted as a sponge for miR-635, increased the expression of NOVA2, and activated the PI3K/AKT signaling pathway. Finally, silencing of circ_0102231 also had obvious antitumor effects in vivo.
Circ_0102231 increased the expression of NOVA2 by interacting with miR-635 to promote the malignant progression of NSCLC.
环状 RNA（circRNAs）参与肿瘤的恶性发展。然而，circ_0102231 在非小细胞肺癌（NSCLC）中的作用机制很少被讨论和报道。
采用实时定量聚合酶链反应（qRT-PCR）检测 NSCLC 组织和细胞中 circ_0102231、miR-635 和 NOVAl 剪接调节因子 2（NOVA2）的表达。采用 Western blot 检测蛋白表达。细胞计数试剂盒-8（CCK8）和 5-乙炔基-2'-脱氧尿苷（EdU）实验检测细胞增殖。血管生成实验检测细胞的血管生成能力。流式细胞术分析细胞凋亡。双荧光素酶报告基因实验和 RNA 免疫沉淀（RIP）实验分析 circ_0102231 与 NOVA2 或 miR-635 的关系。建立体内移植瘤模型，验证 circ_0102231 对肿瘤形成的影响。
circ_0102231 在 NSCLC 组织中异常上调，并与临床分期相关。沉默 circ_0102231 抑制 NSCLC 细胞的增殖和血管生成，但显著促进其凋亡。circ_0102231 与 miR-635、miR-635 与 NOVA2 之间存在靶标结合位点。重要的是，circ_0102231 作为 miR-635 的海绵体，增加了 NOVA2 的表达，并激活了 PI3K/AKT 信号通路。最后，沉默 circ_0102231 也在体内具有明显的抗肿瘤作用。
circ_0102231 通过与 miR-635 相互作用增加 NOVAl 的表达，促进 NSCLC 的恶性进展。
