Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a.
Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a.
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长非编码RNA ATB通过负调控miR-200a促进神经胶质瘤恶性
DOI：
10.1186/s13046-016-0367-2
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发表时间：
2016-06-06
期刊：
影响因子：
--
通讯作者：
Zhao B
中科院分区：
文献类型：
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作者：
Ma CC;Xiong Z;Zhu GN;Wang C;Zong G;Wang HL;Bian EB;Zhao B
背景胶质瘤是脑内最常见、最具侵袭性的原发性恶性肿瘤之一。越来越多的证据表明，异常表达的非编码RNA（ncRNA），包括长链非编码RNA（lncRNA）和微小RNA（miRNAs）参与了肿瘤的发生。方法采用定量逆转录-PCR技术，对TGF-β激活的长链非编码RNA（LncRNA-ATB）在胶质瘤组织和细胞中的表达进行定量分析。分别用sh-ATB、miR-200 a模拟物、miR-200 a抑制剂转染胶质瘤细胞系U251和A172，检测细胞表型和相关分子的表达。结果与正常脑组织相比，ATB在胶质瘤组织和胶质瘤细胞系中的表达均异常上调，ATB高表达的胶质瘤患者的总生存期较短。ATB基因的敲除可显著抑制胶质瘤的恶性程度，包括细胞增殖、集落形成、迁移、体外侵袭和体内异种移植瘤的形成。此外，ATB被证实靶向miR-200 a，并且miR-200 a抑制逆转了ATB敲低对胶质瘤细胞的恶性特征。结论ATB可能通过抑制miR-200 a和促进TGF-β 2的表达而发挥胶质瘤细胞的致瘤作用，可能是胶质瘤治疗的潜在靶点。
BackgroundGlioma is one of the most common and aggressive primary malignant tumor in the brain. Accumulating evidences indicated that aberrantly expressed non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), contribute to tumorigenesis. However, potential mechanisms between lncRNAs and miRNAs in glioma remain largely unknown.MethodsLong non-coding RNA activated by TGF-β (LncRNA-ATB) expression in glioma tissues and cells was quantified by quantitative reverse transcription–PCR. Glioma cell lines U251 and A172 were transfected with sh-ATB, miR-200a mimics, miR-200a inhibitors, after we assayed the cell phenotype and expression of the relevant molecules. Dual-luciferase reporter assay, RIP and a xenograft mouse model were used to examine the expression of sh-ATB and its target gene miR-200a.ResultsATB is abnormally up-regulated both in glioma tissues and cell lines compared with normal brain tissues, and glioma patients with high ATB expression had shorter overall survival time. Knockdown of ATB significantly inhibits glioma malignancy, including cell proliferation, colony formation, migration, invasion in vitro, and the xenograft tumor formation in vivo. In addition, ATB was confirmed to target miR-200a, and miR-200a inhibition reversed the malignant characteristics of ATB knockdown on glioma cells. In particular, ATB may act as a ceRNA, effectively becoming a sink for miR-200a, thereby modulating the derepression of TGF-β2.ConclusionsOur findings suggest that ATB plays an oncogenic role of glioma cells by inhibiting miR-200a and facilitating TGF-β2 in glioma, thereby may represent a potential therapeutic target for the treatment of human glioma.