Laboratory of Radiation Oncology and Radiobiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China.
Beijing Huilongguan Hospital, Peking University Huilongguan School of Clinical Medicine, Beijing 100871, China.
Genes (Basel). 2022 May 10;13(5):846. doi: 10.3390/genes13050846.
Circular RNA (CircRNA) is related to tumor development. Nevertheless, the regulation and function of hsa_circ_0006692 and its interactions with miR-205-5p and in the development of non-small-cell lung cancer (NSCLC) were un-explored. The correlations of expression levels of hsa_circ_0006692 in NSCLC specimens and cells with pathological characteristics were studied. The interactions of hsa_circ_0006692 with miR-205-5p and were assessed with real-time PCR, RNA-binding protein immunoprecipitation (RIP), luciferase reporter, RNA pull-down, and fluorescence in situ hybridization (FISH). The roles of hsa_circ_0006692 on cell growth, invasion, and migration in vitro and metastasis in vivo were evaluated. Hsa_circ_0006692 was over-expressed in 60 cases of NSCLC specimens and cells, which was positively correlated with TNM stage, tumor size, and invasion of the lung basal layer. The results of the in vitro and in vivo studies revealed that the over-expression of hsa_circ_0006692 facilitated NSCLC cell growth, migration, and invasion, cell cycle arrest at the S phase, and the activation of , , and . The results of the dual-luciferase reporter assay, RNA immunoprecipitation, and pull-down assays indicated that hsa_circ_0006692 sponged miR-205-5p, which targeted and facilitated the malignant behaviors of lung cancer cells. Hsa_circ_0006692 modulated EMT of lung cancer cells via the stimulation of , , , and . This study revealed that hsa_circ_0006692 promoted NSCLC progression via enhancing cell growth, invasion, and metastasis through sponging mir-205-5p, up-regulating the downstream oncogene and modulating EMT of lung cancer cells. The circ-0006692/mir-205-5p/ axis might serve as a prognosis biomarker and target for drugs aimed against NSCLC.
环状 RNA (CircRNA) 与肿瘤的发生发展有关。然而，hsa_circ_0006692 的调控机制及其与 miR-205-5p 和 在非小细胞肺癌 (NSCLC) 发生发展中的作用尚未阐明。本研究旨在探讨 hsa_circ_0006692 在 NSCLC 组织和细胞中的表达水平与病理特征的相关性，分析 hsa_circ_0006692 与 miR-205-5p 和 的相互作用，采用实时定量 PCR、RNA 结合蛋白免疫沉淀 (RIP)、荧光素酶报告基因、RNA 下拉实验和荧光原位杂交 (FISH) 等方法检测 hsa_circ_0006692 与 miR-205-5p 和 的相互作用，评估 hsa_circ_0006692 在体外对细胞生长、侵袭和迁移及体内转移的影响。结果显示，在 60 例 NSCLC 组织和细胞中 hsa_circ_0006692 呈高表达，且与 TNM 分期、肿瘤大小及基底膜浸润呈正相关。体外和体内研究结果表明，hsa_circ_0006692 的过表达促进 NSCLC 细胞的生长、迁移和侵袭，细胞周期阻滞在 S 期，同时激活 、 、和 。双荧光素酶报告基因实验、RNA 免疫沉淀和下拉实验结果表明，hsa_circ_0006692 作为 miR-205-5p 的海绵分子，靶向 并促进肺癌细胞的恶性行为。hsa_circ_0006692 通过刺激 、 、 和 调节肺癌细胞的 EMT。本研究表明，hsa_circ_0006692 通过海绵吸附 miR-205-5p 增强下游致癌基因 的表达，促进 NSCLC 细胞的生长、侵袭和转移，从而促进 NSCLC 的进展，并通过刺激 EMT 调节肺癌细胞的 EMT。circ-0006692/mir-205-5p/ 轴可能作为 NSCLC 预后标志物和治疗靶点。
