Abstract Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a high fatality rate in men and women worldwide. Recently, microRNAs (miRNAs) have been reported to be diagnostic biomarkers and therapeutic targets in NSCLC. MiR-223-3p was proved to act as a promoter in NSCLC progression. However, the regulatory mechanism of miR-223-3p in NSCLC remains little known. This study aimed to explore the regulatory mechanism between miR-223-3p and its target gene Ras homolog family member B (RHOB) in NSCLC. The mRNA level of miR-223-3p and RHOB was measured by quantitative reverse transcription PCR. Furthermore, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was conducted to analyze cell apoptosis. Transwell assays and wound healing assay were employed to examine migration and invasion. The target relationship between miR-223-3p and RHOB was predicted by starBase online database and verified by dual-luciferase assay. The protein level of RHOB was tested by western blot. Our data suggested that miR-223-3p was upregulated in NSCLC tissues and cell lines and high level of miR-223-3p contributed to a poor survival in NSCLC patients. Knockdown of miR-223-3p exerted inhibitory effects on NSCLC cell viability, migration, and invasion and promotion effect on cell apoptosis. Furthermore, RHOB was directly targeted by miR-223-3p and constrained NSCLC progression. Moreover, knockdown of RHOB rescued the effect of anti-miR-223-3p on NSCLC progression. In vivo experiments indicated that miR-223-3p deletion suppressed tumor growth. MiR-223-3p could regulate the NSCLC cellular processes through targeting RHOB.

中文翻译：

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MiR-223-3p通过靶向RHOB调节非小细胞肺癌细胞的活力、迁移、侵袭和凋亡


摘要 非小细胞肺癌（NSCLC）是最常见的肺癌类型，在全球男性和女性中死亡率很高。最近，据报道 microRNA (miRNA) 可以作为 NSCLC 的诊断生物标志物和治疗靶点。 MiR-223-3p 被证明可作为 NSCLC 进展的启动子。然而，miR-223-3p在NSCLC中的调控机制仍知之甚少。本研究旨在探讨miR-223-3p及其靶基因Ras同源家族成员B（RHOB）在NSCLC中的调控机制。通过定量逆转录PCR测量miR-223-3p和RHOB的mRNA水平。此外，通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定测定细胞活力。进行流式细胞术分析细胞凋亡。采用Transwell实验和伤口愈合实验来检查迁移和侵袭。通过starBase在线数据库预测miR-223-3p和RHOB之间的靶关系，并通过双荧光素酶测定验证。通过western blot检测RHOB的蛋白水平。我们的数据表明 miR-223-3p 在 NSCLC 组织和细胞系中表达上调，高水平的 miR-223-3p 导致 NSCLC 患者的生存率较差。 miR-223-3p的敲低对NSCLC细胞的活力、迁移和侵袭产生抑制作用，并促进细胞凋亡。此外，RHOB 直接被 miR-223-3p 靶向并限制 NSCLC 进展。此外，敲除 RHOB 可以挽救抗 miR-223-3p 对 NSCLC 进展的影响。体内实验表明，miR-223-3p 缺失可抑制肿瘤生长。 MiR-223-3p可以通过靶向RHOB来调节NSCLC细胞过程。