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SP1上调的LBX2-AS1通过靶向miR-491-5p/LIF轴促进胶质瘤进展。

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

作者信息

Li Wentao, Soufiany Ismatullah, Lyu Xiao, Lu Chenfei, Wei Yutian, Shi Zhumei, You Yongping

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.

Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, Jiangsu, China.

出版信息

J Cancer. 2021 Oct 11;12(23):6989-7002. doi: 10.7150/jca.63289. eCollection 2021.

DOI:10.7150/jca.63289
PMID:34729101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8558668/
Abstract

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. Relative levels of LBX2-AS1 in glioma samples and cell lines were detected by qRT-PCR and FISH. and 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. 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. 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.

摘要

越来越多的证据表明长链非编码RNA（lncRNAs）在肿瘤发生和癌症进展中具有重要作用。LBX2-AS1被鉴定为一种致癌lncRNA，在胃癌和肺癌样本中异常表达。本研究旨在探讨LBX2-AS1在调节胶质瘤增殖和上皮-间质转化（EMT）中的潜在作用及其潜在机制。通过定量逆转录聚合酶链反应（qRT-PCR）和荧光原位杂交（FISH）检测胶质瘤样本和细胞系中LBX2-AS1的相对水平。并在异种移植胶质瘤模型和胶质瘤细胞中检测LBX2-AS1对增殖和EMT的调节作用。通过染色质免疫沉淀（ChIP）评估SP1与LBX2-AS1之间的相互作用。通过生物信息学分析、双荧光素酶报告基因检测、RNA免疫沉淀（RIP）和蛋白质免疫印迹法（Western blot），确定LBX2-AS1和微小RNA-491-5p（miR-491-5p）对靶基因白血病抑制因子（LIF）的调控作用。LBX2-AS1在胶质瘤样本和细胞系中上调，其转录通过与转录因子SP1结合而被促进。作为一种主要分布在细胞质中的lncRNA，LBX2-AS1可吸附miR-491-5p，从而进一步上调LIF。随后激活的LIF/信号转导和转录激活因子3（STAT3）信号通路负责促进胶质瘤的增殖和EMT。在胶质瘤中，SP1上调LBX2-AS1，后者通过靶向miR-491-5p/LIF轴促进胶质瘤进展。鉴于此，LBX2-AS1被认为是胶质瘤的一种新型诊断生物标志物和治疗靶点。

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