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LncRNA NBR2 inhibits epithelial-mesenchymal transition by regulating Notch1 signaling in osteosarcoma cells |
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| Authors: | Weiliang Cai Bowen Wu Zhizhong Li Peiheng He Biao Wang Anlie Cai Xiping Zhang |
| Institution: | 1. Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, China
Weiliang Cai and Bowen Wu contributed equally to this work.;2. Department of Orthopedics, The Affiliated Zhuzhou Hospital, Xiangya Medical College, Central South University, Zhuzhou, China Weiliang Cai and Bowen Wu contributed equally to this work.;3. Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, China;4. Department of Joint Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China;5. Department of Orthopedics, The Affiliated Zhuzhou Hospital, Xiangya Medical College, Central South University, Zhuzhou, China |
| Abstract: | 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. |
| Keywords: | epithelial-mesenchymal transition long noncoding RNA NBR2 Notch1 osteosarcoma |