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circFOXM1 promotes proliferation of non-small cell lung carcinoma cells by acting as a ceRNA to upregulate FAM83D

CircFOXM1 通过作为 ceRNA 上调 FAM83D 促进非小细胞肺癌细胞增殖

  • 影响因子:5.6460
  • DOI:10.1186/s13046-020-01555-5
  • 作者列表:"Chengtao Yu","Zhuoan Cheng","Shaohua Cui","Xiaowei Mao","Botai Li","Yujie Fu","Hui Wang","Haojie Jin","Qing Ye","Xiaojing Zhao","Liyan Jiang","Wenxin Qin
  • 发表时间:2020-04-03
Abstract

Abstract Background 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). Methods 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. Results 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. Conclusions 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.

摘要

文摘背景环状 rna (circular RNAs,circRNAs) 的生物学作用和临床意义在很大程度上仍然未知。在此,我们旨在探讨环状 RNA FOXM1 (circFOXM1) 在非小细胞肺癌 (NSCLC) 中的生物学功能、分子机制和临床意义。方法采用 qRT-PCR 方法检测 48 例配对 NSCLC 标本中 circFOXM1 的表达。通过体外和体内试验探索 circFOXM1 对肿瘤细胞的功能作用。采用转录组测序筛选参与 circFOXM1 调控网络的分子。RNA 免疫沉淀、荧光素酶分析、 RNA 下拉和拯救试验被用来研究 circoxm1 的潜在机制。结果我们发现 circFOXM1 在 NSCLC 组织中显著上调,其上调与 NSCLC 患者的临床分期晚期和预后不良呈正相关。增益或功能丧失试验表明,circFOXM1 促进细胞增殖和细胞周期进程。体内试验表明沉默 circFOXM1 可抑制异种移植肿瘤生长。机械地,转录组测序数据表明沉默 circoxm1 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提示 circFOXM1 可以与 miR-614 结合,FAM83D 是参与 circFOXM1/miR-614 调控网络的必需基因。结论 circfoxm1 通过与 miR-614 相互作用促进 NSCLC 进展,从而使 miR-614 功能失活,从而进一步解除对 FAM83D 的抑制。circFOXM1/miR-614/FAM83D 调控网络可能作为 NSCLC 患者潜在的治疗靶点。

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

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DOI:10.1016/j.annonc.2019.10.022
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