circFOXM1 promotes proliferation of non-small cell lung carcinoma cells by acting as a ceRNA to upregulate FAM83D
circFOXM1 promotes proliferation of non-small cell lung carcinoma cells by acting as a ceRNA to upregulate FAM83D
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circFOXM1作为ceRNA上调FAM83D促进非小细胞肺癌细胞增殖
DOI：
10.1186/s13046-020-01555-5
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发表时间：
2020-03-30
影响因子：
11.3
通讯作者：
Qin, Wenxin
中科院分区：
文献类型：
--
作者：
Yu, Chengtao;Cheng, Zhuoan;Qin, Wenxin
背景环状RNA（circular RNA，circRNA）的生物学作用和临床意义尚不清楚.本研究旨在探讨环状RNA FOXM 1（circFOXM 1）在非小细胞肺癌（NSCLC）中的生物学功能、分子机制及其临床意义。通过体外和体内试验探索circFOXM 1对肿瘤细胞的功能作用。采用转录组测序技术筛选circFOXM 1调控网络相关分子。采用RNA免疫沉淀、荧光素酶分析、RNA pull-down和rescue检测等方法，对circFOXM 1的作用机制进行了研究。结果circFOXM 1在NSCLC组织中表达明显上调，且其表达上调与NSCLC患者的临床分期和预后不良呈正相关。功能获得或丧失试验表明，circFOXM 1促进细胞增殖和细胞周期进展。体内试验表明，沉默circFOXM 1抑制异种移植肿瘤生长。从机制上讲，转录组测序数据表明，沉默circFOXM 1导致细胞周期相关mRNA的下调。结论circFOXM 1通过与miR-614相互作用，使miR-614功能失活，从而进一步解除FAM 83 D的抑制，促进NSCLC的进展。circFOXM 1/miR-614/FAM 83 D调控网络可能成为NSCLC患者潜在的治疗靶点。
BackgroundBiological 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).MethodsExpression 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.ResultsWe 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.ConclusionscircFOXM1promotes 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.