SP1-upregulated LBX2-AS1 promotes the progression of glioma by targeting the miR-491-5p/LIF axis.

SP1-upregulated LBX2-AS1 promotes the progression of glioma by targeting the miR-491-5p/LIF axis.
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SP1上调的LBX2-AS1通过靶向miR-491-5p/LIF轴促进神经胶质瘤的进展

DOI:
10.7150/jca.63289
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发表时间:
2021
期刊:
影响因子:
3.9
通讯作者:
You Y
You Y
中科院分区:
医学3区
文献类型:
--
作者:
Li W;Soufiany I;Lyu X;Lu C;Wei Y;Shi Z;You Y

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背景:越来越多的证据表明lncrna在癌症发生和癌症进展中的重要性。LBX2-AS1是一种在胃癌和肺癌样本中异常表达的致癌lncRNA。本研究旨在探讨LBX2-AS1在胶质瘤中调控增殖和EMT的潜在作用及其机制。方法:采用qRT-PCR和FISH检测胶质瘤样品和细胞系中LBX2-AS1的相对水平。在异种胶质瘤模型和胶质瘤细胞中检测了LBX2-AS1对增殖和EMT的体内外调节作用。通过ChIP评估SP1与LBX2-AS1的相互作用。通过生物信息学分析、双荧光素酶报告基因测定、RIP和Western blot,鉴定了LBX2-AS1和miR-491-5p对靶基因LIF的调控作用。结果:LBX2-AS1在胶质瘤样品和细胞系中表达上调,并通过与转录因子SP1结合促进其转录。LBX2-AS1作为一种主要分布在细胞质中的lncRNA,通过海绵miR-491-5p进一步上调LIF。随后激活的LIF/STAT3信号负责促进胶质瘤的增殖和EMT。结论:在胶质瘤中,SP1上调LBX2-AS1,通过靶向miR-491-5p/LIF轴促进胶质瘤的进展。鉴于此,LBX2-AS1被认为是胶质瘤新的诊断生物标志物和治疗靶点。
Background: Mounting evidences have shown the importance of lncRNAs in carcinogenesis and cancer progression. LBX2-AS1 is identified as an oncogenic lncRNA that is abnormally expressed in gastric cancer and lung cancer samples. This study aims to explore the potential role of LBX2-AS1 in regulating proliferation and EMT in glioma, and the underlying mechanism. Methods: Relative levels of LBX2-AS1 in glioma samples and cell lines were detected by qRT-PCR and FISH. In vivo and in vitro regulatory effects of LBX2-AS1 on proliferation and EMT were examined in the xenograft glioma model and glioma cells. The interaction between SP1 and LBX2-AS1 was assessed by ChIP. Through bioinformatic analyses, dual-luciferase reporter assay, RIP and Western blot, the regulation of LBX2-AS1 and miR-491-5p on the target gene LIF was identified. Results: LBX2-AS1 was upregulated in glioma samples and cell lines, and its transcription was promoted by binding to the transcription factor SP1. As a lncRNA mainly distributed in the cytoplasm, LBX2-AS1 sponge miR-491-5p to further upregulate LIF. The subsequent activated LIF/STAT3 signaling was responsible for promoting proliferation and EMT in glioma. Conclusion: LBX2-AS1 is upregulated by SP1 in glioma, which promotes the progression of glioma by targeting the miR-491-5p/LIF axis. In view of this, LBX2-AS1 is suggested as a novel diagnostic biomarker and therapeutic target of glioma.
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