LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway.
LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway.
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LncRNA BCYRN1 通过与 miR-619-5p 竞争性结合调节 CUEDC2 表达和 PTEN/AKT/p21 通路来抑制胶质瘤肿瘤发生
DOI：
10.1038/s41388-020-01466-x
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发表时间：
2020-11
期刊：
影响因子：
8
通讯作者：
Niu C
中科院分区：
文献类型：
--
作者：
Mu M;Niu W;Zhang X;Hu S;Niu C
脑胶质瘤是中枢神经系统最常见的恶性肿瘤。改变的长链非编码RNA（lncRNA）在癌症的生理和病理过程中起着调节作用。本研究发现了一种差异表达的lncRNA--脑胞质RNA 1（brain cytoplasmic RNA 1，BCYRN 1），并阐明了其在胶质瘤发生发展中的作用及其分子机制。制备三份来自胶质瘤患者的新鲜肿瘤组织和三份来自颅脑外伤患者的正常脑组织用于高通量RNA测序。通过RT-qPCR鉴定胶质瘤样品和对照中的差异RNA转录物和BCYRN 1。通过CCK-8、集落形成实验、流式细胞术、TUNEL实验、细胞迁移实验、创伤愈合实验和异种移植模型研究BCYRN 1在体内外的生物学功能。进行了各种生物信息学分析、双荧光素酶报告基因测定、生物素化RNA下拉测定和拯救实验，以揭示竞争性内源RNA（ceRNA）的潜在机制。183个lncRNA被鉴定为在胶质瘤中具有显著的失调，并且随机选择的差异RNA通过RT-qPCR进一步证实。其中，BCYRN 1是下调最多的lncRNA，其低表达与胶质瘤进展呈正相关。在功能上，BCYRN 1过表达抑制胶质瘤细胞系中的细胞增殖、迁移，而BCYRN 1缺失导致相反的方式。进一步证实miR-619- 5 p是BCYRN 1的直接靶点。从机制上讲，miR-619- 5 p特异性靶向CUE结构域蛋白2（CUEDC 2），BCYRN 1/miR-619- 5 p通过以CUEDC 2依赖性方式灭活PTEN/AKT/p21通路抑制胶质瘤发生。总体而言，我们的数据表明，BCYRN 1的表达减少与胶质瘤患者预后不良相关。BCYRN 1作为一种ceRNA，通过海绵状的miR-619- 5 p调控CUEDC 2的表达和PTEN/AKT/p21通路，抑制胶质瘤的进展。本研究结果提示BCYRN 1具有肿瘤抑制作用，可能成为胶质瘤诊断和治疗的候选基因。
Glioma is the most common malignant tumor in the central nervous system. Altered long noncoding RNAs (lncRNAs) are playing regulatory roles in physiological and pathogenic processes in cancer. Here, we uncovered a differentially expressed lncRNA called brain cytoplasmic RNA 1 (BCYRN1), and elucidated its function and molecular mechanism in the progression and development of glioma. Three fresh tumor tissues from glioma patients and three normal brain tissues from craniocerebral trauma patients were prepared for high-throughput RNA sequencing. Differential RNA transcripts and BCYRN1 were identified by RT-qPCR in glioma samples and controls. CCK-8, colony formation assays, flow cytometry, TUNEL assays, cell migration assays, wound-healing assays, and xenograft model were established to investigate the biological function of BCYRN1 both in vitro and in vivo. Various bioinformatics analysis, dual-luciferase reporter assays, biotinylated RNA pulldown assays, and rescue experiments were conducted to reveal the underlying mechanisms of competitive endogenous RNAs (ceRNAs). 183 lncRNAs were identified with significant dysregulation in glioma and randomly selected differential RNAs were further confirmed by RT-qPCR. Among them, BCYRN1 was the most downregulated lncRNA, and its low expression positively correlated with glioma progression. Functionally, BCYRN1 overexpression inhibited cell proliferation, migration in glioma cell lines, whereas BCYRN1 depletion resulted in the opposite way. MiR-619-5p was further confirmed as the direct target of BCYRN1. Mechanistically, miR-619-5p specifically targeted the CUE domain containing protein 2 (CUEDC2), and BCYRN1/miR-619-5p suppressed glioma tumorigenesis by inactivating PTEN/AKT/p21 pathway in a CUEDC2-dependent manner. Overall, our data presented that the reduced expression of BCYRN1 was associated with poor patient outcome in glioma. BCYRN1 functioned as a ceRNA to inhibit glioma progression by sponging miR-619-5p to regulate CUEDC2 expression and PTEN/AKT/p21 pathway. Our results indicated that BCYRN1 exerted tumor suppressor potential and might be a candidate in the diagnosis and treatment of glioma.
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影响因子：
28.2
作者：
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通讯作者：
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影响因子：
16.8
作者：
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影响因子：
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