| Research background: Glioma characterized by local infiltration and neovascularization is the most common primary tumor of the central nervous system.Among which,glioblastoma(GBM)is the most malignant,accounting for 50% of gliomas,and the 5-year survival rate is less than 10%.Glioma is known to be highly heterogeneous,even different cells from the same tumor can exhibit distinctive patterns of gene expression and biological behavior.Therefore,it is a huge challenge to enhance the diagnostic accuracy of glioma,and thus performs targeted therapy to improve the clinical outcome.Lnc RNAs(long non-coding RNAs)are over 200 nucleotides long,which are functional in epigenetic regulation,histone modification,transcription control and RNA metabolism.Current evidences have proven the regulatory effects of lnc RNAs on cancer progression.L Salmena et al.first proposed the ce RNA theory,in which lnc RNAs exert a sponge effect on mi RNAs,therefore upregulating m RNAs downstream to them.Based on this theory,the lnc RNA-mi RNA-m RNA axis has been widely explored in multiple types of cancers.It is reported that MALAT1 upregulates VEGF,Slug and Twist by exerting the sponge effect on mi R-126-5p,thus triggering EMT and angiogenesis in colorectal cancer.Serving as a vital ce RNA,CRNDE activates the PIWIL4/STAT3 signaling pathway through mi R-384,which further accelerates the proliferative and invasive capacities of glioma cells.Recently,LBX2-AS1 has been confirmed as an oncogenic lnc RNA.LBX2-AS1 is also upregulated in glioma samples and correlated to patient prognosis,but its role in glioma remains unclear.This study first detected the differential level of LBX2-AS1 in glioma tissues,its oncogenic role and the underlying mechanism were further explored.Methods: 1.By analyzing the RNA-seq data of glioma samples in TCGA,CGGA and GEO(GSE151352)datasets,abnormal expression of LBX2-AS1 in glioblastoma samples was screened out.2.Relative levels of LBX2-AS1 in GBM samples and cell lines were detected by q RT-PCR and FISH.3.The regulatory effects of LBX2-AS1 on epithelial-mesenchymal transformation(EMT)and angiogenesis in glioma were verified by a series of cell function experiments.4.The interaction between SP1 and LBX2-AS1 was assessed by Ch IP.5.Through bioinformatic analyses,dual-luciferase reporter assay,RIP and Western blot,the regulation of LBX2-AS1 and mi R-491-5p on leukemia Inhibitory factor(LIF)was identified.6.The promotion effects of LBX2-AS1 on glioma growth in vivo was tested by xenograft model.Results: 1 LBX2-AS1 was upregulated in GBM samples and cell lines.2 LBX2-AS1 promoted the progression of glioma by regulating EMT and angiogenesis.3 Transcription factor SP1 regulated expression of LBX2-AS1 by binding to its promoter region.4 As a lnc RNA mainly distributed in the cytoplasm,LBX2-AS1 upregulated LIF,and activated the LIF/STAT3 signaling by exerting the mi RNA sponge effect on mi R-491-5p,thus promoting EMT and angiogenesis in glioma.5 In vivo results indicate that LBX2-AS1 promotes glioma progression and is an adverse factor for prognosis.Conclusion:Upregulated by SP1,LBX2-AS1 regulates EMT and angiogenesis by targeting mi R-491-5p/LIF axis,thus promoting malignant progression of glioma.It is suggested that LBX2-AS1 may be a novel diagnostic biomarker and therapeutic target of glioma. |
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