LncRNA NBR2 inhibits epithelial-mesenchymal transition by regulating Notch1 signaling in osteosarcoma cells
LncRNA NBR2 inhibits epithelial-mesenchymal transition by regulating Notch1 signaling in osteosarcoma cells
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DOI：
10.1002/jcb.27508
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发表时间：
2019-02-01
影响因子：
4
通讯作者：
Zhang, Xiping
中科院分区：
文献类型：
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作者：
Cai, Weiliang;Wu, Bowen;Zhang, Xiping
长链非编码RNA（longnoncodingRNA，lncRNA）在肿瘤发生中的作用日益重要，有望成为肿瘤治疗的新生物标志物。最近的研究表明，lncRNA NBR 2（BRCA 1基因2的邻居），一种新发现的lncRNA，在几种癌症中减少;然而，NBR 2在骨肉瘤发生中的作用尚未阐明。在我们的研究中，我们发现NBR 2在骨肉瘤组织中表达下调，与NBR 2高表达的骨肉瘤病例相比，NBR 2低表达的骨肉瘤病例的总生存时间较短。NBR 2过表达抑制骨肉瘤细胞增殖、侵袭和迁移，但不增加细胞凋亡。此外，RNA结合蛋白免疫沉淀试验证实，NBR 2直接结合到Notch 1蛋白。此外，Notch 1在NBR 2过表达的骨肉瘤细胞中的过表达逆转了NBR 2对细胞增殖、侵袭、迁移和上皮间质转化的影响。体内实验结果表明，NBR 2过表达抑制了接种骨肉瘤细胞的裸鼠的肿瘤生长。NBR 2过表达还抑制Notch 1、N-cadherin和vimentin的信使RNA（mRNA）表达，并增加肿瘤组织中E-cadherin的mRNA表达。这些数据表明，NBR 2作为一个抑癌基因在骨肉瘤和抑制骨肉瘤细胞的增殖，侵袭和迁移。本研究为骨肉瘤的治疗提供了新的思路和策略。
Long noncoding RNAs (lncRNAs) have been identified to have increasingly important roles in tumorigenesis, and they may serve as novel biomarkers for cancer therapy. Recent studies have demonstrated that lncRNA NBR2 (neighbor of BRCA1 gene 2), a novel identified lncRNA, is decreased in several cancers; however, the role of NBR2 in the development of osteosarcoma has not been elucidated. In our study, we found that NBR2 expression was downregulated in osteosarcoma tissues, and osteosarcoma cases with lower NBR2 expression exhibited a shorter overall survival time compared with those with higher NBR2 expression. NBR2 overexpression inhibited osteosarcoma cell proliferation, invasion, and migration but did not increase apoptosis. Furthermore, RNA-binding protein immunoprecipitation assays confirmed that NBR2 directly binds to Notch1 protein. Furthermore, overexpression of Notch1 in NBR2-overexpressing osteosarcoma cells reversed the effects of NBR2 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition. The in vivo results showed that NBR2 overexpression inhibited tumor growth in nude mice that were inoculated with osteosarcoma cells. NBR2 overexpression also suppressed the messenger RNA (mRNA) expression of Notch1, N-cadherin, and vimentin and increased the mRNA expression of E-cadherin in the tumor tissues. These data indicated that NBR2 served as a tumor suppressor gene in osteosarcoma and inhibited osteosarcoma cell proliferation, invasion, and migration. The current study provides a novel insight and treatment strategy for osteosarcoma.