Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.
Department of Oncology, General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin, Heilongjiang, China.
J Biochem Mol Toxicol. 2024 Apr;38(4):e23684. doi: 10.1002/jbt.23684.
Lung cancer is the leading cause of cancer-related deaths worldwide. Circular RNA (circRNA) circ_0088036 is a recently discovered circRNA known for its roles in rheumatoid arthritis. The study aimed to study the function of circ_0088036 in lung adenocarcinoma (LUAD). Circ_0088036 expressions were analyzed in the Gene Expression Omnibus (GEO) database. The relationship between circ_0088036 expressions and clinicopathological data of LUAD was assessed. The messenger RNA and protein levels were analyzed by quantitative real-time polymerase chain reaction and Western blot. Cell viability, apoptosis, and invasion were tested by Cell Counting Kit-8, flow cytometry, and transwell assay. The direct interaction between microRNA-203 (miR-203) and circ_0088036 or specificity protein 1 (SP1) was confirmed by dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assays. Circ_0088036 was overexpressed in LUAD from the analysis of the GEO database. The poor prognosis was found in the patients with high expressions of circ_0088036. The level of Circ_0088036 was increased in LUAD tissues and cells. In terms of function, the deletion of circ_0088036 inhibited LUAD tumorigenesis in vitro by repressing cell growth, invasion, and epithelial-mesenchymal transition (EMT). In mechanism, circ_0088036 could competitively sponge miR-203, thereby affecting the expressions of the target gene SP1. In addition, lessening of miR-203 and enlarging of SP1 could eliminate the anticancer effect of short hairpin RNA-circ_0088036 on LUAD cells. Besides, the knockout of circ_0088036 hindered the growth of xenografted tumors in vivo. Circ_0088036 promoted the LUAD cell growth, invasion, and EMT via modulating the miR-203/SP1 axis in LUAD.
肺癌是全球癌症相关死亡的主要原因。环状 RNA（circRNA）circ_0088036 是一种最近发现的环状 RNA，其在类风湿关节炎中的作用已被广泛研究。本研究旨在研究 circ_0088036 在肺腺癌（LUAD）中的功能。通过基因表达综合数据库（GEO）数据库分析 circ_0088036 的表达。评估 circ_0088036 表达与 LUAD 临床病理数据的关系。通过实时定量聚合酶链反应和 Western blot 分析信使 RNA 和蛋白水平。通过细胞计数试剂盒-8、流式细胞术和 Transwell 测定检测细胞活力、凋亡和侵袭。通过双荧光素酶报告基因检测、RNA 下拉和 RNA 免疫沉淀实验证实了 microRNA-203（miR-203）与 circ_0088036 或特异性蛋白 1（SP1）之间的直接相互作用。通过 GEO 数据库分析发现，circ_0088036 在 LUAD 中过表达。高表达 circ_0088036 的患者预后不良。circ_0088036 在 LUAD 组织和细胞中水平升高。就功能而言，circ_0088036 的缺失通过抑制细胞生长、侵袭和上皮-间充质转化（EMT）来抑制体外 LUAD 肿瘤发生。在机制上，circ_0088036 可以竞争性地吸收 miR-203，从而影响靶基因 SP1 的表达。此外，减少 miR-203 和增加 SP1 可以消除短发夹 RNA-circ_0088036 对 LUAD 细胞的抗癌作用。此外，circ_0088036 的敲除阻碍了体内异种移植肿瘤的生长。circ_0088036 通过调节 miR-203/SP1 轴促进 LUAD 细胞的生长、侵袭和 EMT。
