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AC016405.3 a novel long noncoding RNA acts as a tumor suppressor through modulation of TET2 by microRNA‐19a‐5p sponging in glioblastoma

机译:AC016405.3是一种新型的长非编码RNA通过胶质母细胞瘤中的microRNA-19a-5p海绵调控TET2的表达而起到抑癌作用

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摘要

Long non‐coding RNAs (lncRNAs) are crucial regulators in various malignancies including glioblastoma multiforme (GBM). In the present study, we screened out a new lncRNA, , through a previous genome‐wide lncRNA microarray analysis in GBM. It showed that was downregulated in GBM tissue specimens and cell lines, and it also illustrated that the downregulated was closely correlated with several aggressive features of patients with GBM. Functionally, we found that overexpression of suppressed GBM cells’ proliferation and metastasis using a gain of function experiment. We further showed that microRNA (miR)‐19a‐5p, a carcinogenic miRNA, was a downstream miRNA of . was revealed as a target of miR‐19a‐5p, and overexpression of miR‐19a‐5p reversed the inhibitive effect of on GBM cell proliferation and metastasis. Furthermore, a novel downstream gene of miR‐19a‐5p, TET2, was identified through a constructed microarray analysis. We showed that TET2 was downregulated in GBM and was involved in miR‐19a‐5p‐mediated proliferation and metastasis by directly being targeted. Finally, through a western blot assay and a series of functional CCK‐8 and metastatic assays, we showed that suppressed proliferation and metastasis through modulation of TET2 by sponging of miR‐19a‐5p in GBM cells. In summary, the findings of the current study identified a novel lncRNA and illustrated that , acting as an anti‐oncogene, suppressed GBM cell proliferation and metastasis by regulating TET through miR‐19a‐5p sponging. Our present study might provide a new axis in the molecular treatment of GBM.
机译:长的非编码RNA(lncRNA)是包括多形性胶质母细胞瘤(GBM)在内的各种恶性肿瘤的关键调控因子。在本研究中,我们通过GBM中以前的全基因组lncRNA微阵列分析筛选出了新的lncRNA。它表明在GBM组织标本和细胞系中该基因被下调,并且还表明该下调与GBM患者的几种侵袭性特征密切相关。在功能上,我们通过功能增益实验发现抑制的GBM细胞的过度表达和增殖和转移。我们进一步表明,致癌性miRNA microRNA(miR)-19a-5p是的下游miRNA。被揭示为miR-19a-5p的靶标,而miR-19a-5p的过表达逆转了其对GBM细胞增殖和转移的抑制作用。此外,通过构建的微阵列分析鉴定出了miR-19a-5p的新型下游基因TET2。我们表明,TET2在GBM中被下调,并通过直接靶向而参与了miR-19a-5p介导的增殖和转移。最后,通过蛋白质印迹试验以及一系列功能性CCK-8和转移试验,我们证明了通过在GBM细胞中浸润miR-19a-5p可以通过调节TET2抑制增殖和转移。总而言之,当前研究的结果鉴定出了一种新型的lncRNA,并说明了它作为一种抗癌基因,可通过miR-19a-5p海绵调控TET抑制GBM细胞的增殖和转移。我们目前的研究可能为GBM的分子治疗提供新的思路。

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