Biological role and clinical significance of circular RNAs (circRNAs) remain largely unknown. Herein, we aimed to investigate biological function, molecular mechanism, and clinical significance of a circular RNA FOXM1 (circFOXM1) in non-small cell lung cancer (NSCLC). Expression of circFOXM1 was measured in 48 paired samples of NSCLC by qRT-PCR. Functional roles of circFOXM1 on tumor cells were explored by in vitro and in vivo assays. Transcriptome sequencing was employed to screen the molecules involved in circFOXM1 regulatory network. RNA immunoprecipitation, luciferase analysis, RNA pull-down, and rescue assay were used to investigate potential mechanisms of circFOXM1. We found that circFOXM1 was significantly upregulated in NSCLC tissues, and its upregulation was positively correlated with advanced clinical stage and poor prognosis of NSCLC patients. Gain or loss-of-function assay showed that circFOXM1 promoted cell proliferation and cell cycle progression. In vivo assays showed that silencing circFOXM1 inhibited xenograft tumor growth. Mechanically, transcriptome sequencing data indicated that silencing circFOXM1 led to the downregulation of cell cycle-related mRNAs. RNA pull-down and dual-luciferase reporter assay suggested that circFOXM1 could bind to miR-614, and FAM83D was an essential gene involved in the circFOXM1/miR-614 regulatory network. circFOXM1promotes NSCLC progression by interacting with miR-614 and thus inactivating the function of miR-614, which will further release the suppression of FAM83D. circFOXM1/miR-614/FAM83D regulatory network may serve as a potential therapeutic target for NSCLC patients.

中文翻译：

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circFOXM1通过作为ceRNA来上调FAM83D来促进非小细胞肺癌细胞的增殖

环状RNA（circRNA）的生物学作用和临床意义仍然未知。在本文中，我们旨在研究非小细胞肺癌（NSCLC）中环状RNA FOXM1（circFOXM1）的生物学功能，分子机制和临床意义。通过qRT-PCR在48个配对的NSCLC样品中测量了circFOXM1的表达。通过体外和体内试验探索了circFOXM1在肿瘤细胞上的功能作用。转录组测序用于筛选circFOXM1调控网络中涉及的分子。RNA免疫沉淀，荧光素酶分析，RNA下拉和救援测定被用来研究circFOXM1的潜在机制。我们发现circFOXM1在NSCLC组织中显着上调，其上调与NSCLC患者的临床晚期及预后不良呈正相关。增益或功能丧失测定表明circFOXM1促进细胞增殖和细胞周期进程。体内实验表明沉默circFOXM1抑制异种移植肿瘤的生长。在机械上，转录组测序数据表明沉默circFOXM1导致细胞周期相关mRNA的下调。RNA下拉和双荧光素酶报告基因检测表明circFOXM1可以与miR-614结合，而FAM83D是参与circFOXM1 / miR-614调控网络的必需基因。circFOXM1通过与miR-614相互作用并因此使miR-614的功能失活而促进NSCLC进程，这将进一步释放FAM83D的抑制作用。