Department of Interventional Radiology, The first affiliated hospital of Zhengzhou University, Zhengzhou City, PR. China.
Cancer Biol Ther. 2020;21(2):113-121. doi: 10.1080/15384047.2019.1669995. Epub 2019 Oct 10.
Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that are demonstrated to be potent regulators in the development of various types of human cancers, including non-small cell lung cancer (NSCLC). In the present study, the level of circRNA-HIPK3 were measured by Taq-man based quantitative real-time PCR (qRT-PCR) analysis in both NSCLC patient specimens and cells, which showed that circRNA-HIPK3 was upregulated in both NSCLC tissues and cell lines. Cell counting kit-8 (CCK-8), migration and flow-cytometry assays indicated that circRNA-HIPK3 participated in the regulation of the proliferation, migration, invasion and apoptosis of NSCLC cells. MiR-193a expression was increased by circHIPK3 silencing. We then showed that miR-149 interacts with FOXM1 by binding to the 3'-untranslated region (UTR). Further, ectopic overexpression of miR-149 by transfecting miR-149 mimics significantly inhibited growth, migration and invasion of HSCLCs, which was found to be mediated through FOXM1. Moreover, miR-149 overexpression decreases the viability and proliferation of HSCLCs. Therefore, our data suggest that circHIPK3 regulates the function of NSCLCs through miR-149-mediated FOXM1 expression regulation, potentially providing a novel insight into the pathogenesis of NSCLC.
环状 RNA（circRNAs）是一类内源性非编码 RNA，已被证明在多种类型的人类癌症（包括非小细胞肺癌（NSCLC））的发展中具有强大的调控作用。在本研究中，通过 Taqman 定量实时 PCR（qRT-PCR）分析测量了 NSCLC 患者标本和细胞中的 circRNA-HIPK3 水平，结果显示 circRNA-HIPK3 在 NSCLC 组织和细胞系中均上调。细胞计数试剂盒-8（CCK-8）、迁移和流式细胞术分析表明，circRNA-HIPK3 参与了 NSCLC 细胞的增殖、迁移、侵袭和凋亡的调节。circHIPK3 沉默后 miR-193a 的表达增加。然后，我们表明 miR-149 通过结合 3'-非翻译区（UTR）与 FOXM1 相互作用。进一步，通过转染 miR-149 模拟物过表达 miR-149 显著抑制 HSCLCs 的生长、迁移和侵袭，这被发现是通过 FOXM1 介导的。此外，miR-149 的过表达降低了 HSCLCs 的活力和增殖。因此，我们的数据表明 circHIPK3 通过 miR-149 介导的 FOXM1 表达调控来调节 NSCLC 的功能，这可能为 NSCLC 的发病机制提供了新的见解。
