Abstract：
Circular RNAs (circRNAs) have been widely involved in the malignant development of human cancers. Circ_0001715 was aberrantly upregulated in non-small cell lung cancer (NSCLC). However, circ_0001715 function has never been researched. This study was designed to investigate the role and mechanism of circ_0001715 in NSCLC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to examine the levels of circ_0001715, microRNA-1249-3p (miR-1249-3p) and Fibroblast Growth Factor 5 (FGF5). The proliferation detection was conducted using colony formation assay and EdU assay. Cell apoptosis was analyzed via flow cytometry. Wound healing assay and transwell assay were used for determination of migration and invasion, respectively. The protein levels were measured through western blot. Target analysis was carried out via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft tumor model was established in mice for in vivo research. The significant upregulation of circ_0001715 was detected in NSCLC samples and cells. Circ_0001715 knockdown induced the inhibitory effects on proliferation, migration and invasion but the promoting effect on apoptosis of NSCLC cells. Circ_0001715 could interact with miR-1249-3p. The regulatory role of circ_0001715 was achieved by sponging miR-1249-3p. Furthermore, miR-1249-3p targeted FGF5 and miR-1249-3p acted as a cancer inhibitor by targeting FGF5. Moreover, circ_0001715 upregulated the FGF5 level via targeting miR-1249-3p. In vivo assay showed that circ_0001715 promoted the NSCLC progression through the miR-1249-3p/FGF5 axis. The current evidence elucidated that circ_0001715 served as an oncogenic regulator in NSCLC progression by depending on the miR-1249-3p/FGF5 axis.
摘要：
环状RNA（circularRNAs，circRNAs）已广泛参与人类癌症的恶性发展。Circ_0001715在非小细胞肺癌（NSCLC）中异常上调。然而,circ_0001715函数从未被研究过。本研究旨在探讨circ_0001715在非小细胞肺癌中的作用及机制。进行逆转录-定量聚合酶链反应(RT-qPCR)以检查circ_0001715、microRNA-1249-3p(miR-1249-3p)和成纤维细胞生长因子5(FGF5)的水平。使用集落形成测定和EdU测定进行增殖检测。通过流式细胞术分析细胞凋亡。伤口愈合试验和transwell试验用于测定迁移和侵袭，分别。通过蛋白质印迹测量蛋白质水平。通过双荧光素酶报告基因测定和RNA免疫沉淀(RIP)测定进行靶标分析。在小鼠中建立异种移植肿瘤模型用于体内研究。在NSCLC样品和细胞中检测到circ_0001715的显著上调。Circ_0001715敲低诱导对增殖的抑制作用，但对非小细胞肺癌细胞的迁移和侵袭有促进作用。Circ_0001715可以与miR-1249-3p相互作用。circ_0001715的调节作用是通过生成miR-1249-3p来实现的。此外，miR-1249-3p靶向FGF5和miR-1249-3p通过靶向FGF5充当癌症抑制剂。此外，circ_0001715通过靶向miR-1249-3p上调FGF5水平。体内测定显示circ_0001715通过miR-1249-3p/FGF5轴促进NSCLC进展。目前的证据阐明了circ_0001715通过依赖于miR-1249-3p/FGF5轴在NSCLC进展中充当致癌调节因子。
