Long non-coding RNA HCG11 modulates glioma progression through cooperating with miR-496/CPEB3 axis
Long non-coding RNA HCG11 modulates glioma progression through cooperating with miR-496/CPEB3 axis
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DOI：
10.1111/cpr.12615
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发表时间：
2019-07-16
影响因子：
8.5
通讯作者：
Wang, Zhiqiang
中科院分区：
文献类型：
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作者：
Chen, Yangzong;Bao, Chunchun;Wang, Zhiqiang
目的 据广泛报道，长链非编码 RNA (lncRNA) 可以参与人类癌症的多种生物学过程。据报道，lncRNA HLA 复合物组 11 (HCG11) 在人类癌症中作为肿瘤抑制因子。本研究重点探讨HCG11在胶质瘤中的功能和机制。材料和方法 基于癌症基因组图谱 (TCGA) 数据集和 qRT-PCR 分析，在神经胶质瘤样本中鉴定了 HCG11 的表达模式。通过机制实验确定了与 HCG11 下调相关的机制。进行功能获得测定以鉴定 HCG11 在神经胶质瘤进展中的功能。采用基于荧光素酶报告基因实验、RIP实验和pull-down实验的机制研究探讨HCG11的下游分子机制。根据救援实验分析了分子途径在神经胶质瘤进展中的作用。结果 与正常样本相比，HCG11在胶质瘤样本中表达水平较低。 FOXP1可以与HCG11和转录失活的HCG11结合。 HCG11的过度表达有效抑制细胞增殖、诱导细胞周期停滞并促进细胞凋亡。 HCG11 主要富集于神经胶质瘤细胞的细胞质中，并通过海绵 micro-496 充当竞争性内源 RNA (ceRNA)，从而上调细胞质多聚腺苷酸化元件结合蛋白 3 (CPEB3)。 CEPB3 和 miR-496 参与 HCG11 介导的神经胶质瘤进展。结论 HCG11通过调节miR-496/CPEB3轴抑制胶质瘤进展。
Objectives It has been widely reported that long non-coding RNAs (lncRNAs) can participate in multiple biological processes of human cancers. lncRNA HLA complex group 11 (HCG11) has been reported in human cancers as a tumour suppressor. This study focused on investigating the function and mechanism of HCG11 in glioma. Materials and methods Based on The Cancer Genome Atlas (TCGA) data set and qRT-PCR analysis, the expression pattern of HCG11 was identified in glioma samples. The mechanism associated with HCG11 downregulation was determined by mechanism experiments. Gain-of-function assays were conducted for the identification of HCG11 function in glioma progression. Mechanism investigation based on the luciferase reporter assay, RIP assay and pull-down assay was used to explore the downstream molecular mechanism of HCG11. The role of molecular pathway in the progression of glioma was analysed in accordance with the rescue assays. Results HCG11 was expressed at low level in glioma samples compared with normal samples. FOXP1 could bind with HCG11 and transcriptionally inactivated HCG11. Overexpression of HCG11 efficiently suppressed cell proliferation, induced cell cycle arrest and promoted cell apoptosis. HCG11 was predominantly enriched in the cytoplasm of glioma cells and acted as a competing endogenous RNAs (ceRNAs) by sponging micro-496 to upregulate cytoplasmic polyadenylation element binding protein 3 (CPEB3). CEPB3 and miR-496 involved in HCG11-mediated glioma progression. Conclusions HCG11 inhibited glioma progression by regulating miR-496/CPEB3 axis.