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HOTAIR promotes osteosarcoma development by sponging miR-217 and targeting ZEB1
Authors:Bing Wang  Xing-Long Qu  Jiaxiang Liu  Junhui Lu  Zong-Yu Zhou
Institution:1. Department of Oncological Surgery, Minhang Branch, Cancer Hospital, Fudan University, Shanghai, China

Bing Wang and Xing-Long Qu are co-first authors.;2. Shanghai Jiaotong University School of Medicine, Shanghai, China;3. Department of Rheumatology, Huai‘an Second People's Hospital and The Affiliated Huai‘an Hospital of Xuzhou Medical University, Huai‘an, China;4. Department of Orthopedics, Huaiyin Hospital of Huai'an City, Huai'an, China

Abstract:Long noncoding RNAs (lncRNAs) have drawn increasing attention because of the role which they play in various diseases, including osteosarcoma. So far, the function and mechanism of HOTAIR in osteosarcoma are unclear. In our study, we observed that HOTAIR was elevated accompanied with a decrease of miR-217 and an increase of ZEB1 in human osteosarcoma cells including U2OS, MG63, Saos-2, and SW1353 compared with human osteoblast cell line hFOB. In addition, the subsequent functional assay exhibited that silencing HOTAIR could significantly repress osteosarcoma cell growth, migration, invasion, and induce cell apoptosis capacity, which indicated that HOTAIR exerted an oncogenic role in osteosarcoma. Moreover, it was revealed by using bioinformatics analysis that HOTAIR can be targeted by microRNA-217 (miR-217). miR-217 has been recognized as a crucial tumor suppressive gene in cancers. We verified that mimics of miR-217 were able to suppress the osteosarcoma development. Furthermore, real-time quantitative PCR showed that HOTAIR siRNA increased miR-217 expression. Besides these, ZEB1 was identified as a downstream gene of miR-217 and we found that HOTAIR can mediate osteosarcoma progress by upregulating ZEB1 expression via acting as a competitive endogenous RNA (ceRNA) via miR-217. Taken these together, our findings in this study indicated that HOTAIR/miR-217/ZEB1 axis, as a novel research point can provide new insights into molecular mechanism of osteosarcoma development.
Keywords:HOTAIR  miR-217  osteosarcoma  ZEB1
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