Oncotarget

Research Papers:

MicroRNA-106b inhibits osteoclastogenesis and osteolysis by targeting RANKL in giant cell tumor of bone

Ting Wang _, Huabin Yin, Jing Wang, Zhenxi Li, Haifeng Wei, Zhi’an Liu, Zhipeng Wu, Wangjun Yan, Tielong Liu, Dianwen Song, Xinghai Yang, Quan Huang, Wang Zhou and Jianru Xiao

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Oncotarget. 2015; 6:18980-18996. https://doi.org/10.18632/oncotarget.4223

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Abstract

Ting Wang1,*, Huabin Yin1,*, Jing Wang1,2,*, Zhenxi Li1, Haifeng Wei1, Zhi’an Liu2, Zhipeng Wu1, Wangjun Yan1, Tielong Liu1, Dianwen Song1, Xinghai Yang1, Quan Huang1, Wang Zhou1 and Jianru Xiao1

1 Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China

Department of Anatomy, Xuzhou Medical College, Xuzhou, China

* These authors have contributed equally to this work, and all should be considered first author

Correspondence to:

Jianru Xiao, email:

Wang Zhou, email:

Keywords: giant cell tumor of bone, miR-106b, RANKL, osteoclastogenesis, osteolysis

Received: March 22, 2015 Accepted: May 13, 2015 Published: May 22, 2015

Abstract

Giant cell tumor (GCT) of bone consists of three major cell types: giant cells, monocytic cells, and stromal cells. From microarray analysis, we found that miR-106b was down-regulated in GCT clinical samples and further determined by fluorescence in situ hybridization. In addition, the expression of novel potential target of miR-106b, RANKL, was elevated in GCT along with previously determined targets in other tumors such as IL-8, MMP2 and TWIST. In a RANKL 3’UTR luciferase reporter assays, agomiR-106b repressed the luciferase activity and the effect was eliminated when the targeting site in the reporter was mutated, suggesting a direct regulation of miR-106b on RANKL mRNA. Moreover, overexpression of miR-106b in GCTSCs through TALEN-mediated site-specific knockin clearly inhibited osteoclastogenesis and osteolysis. By grafting the GCT onto the chick CAM, we confirmed the inhibitory effect of miR-106b on RANKL expression and giant cell formation. Furthermore, in an OVX mouse model, silencing of miR-106b increased RANKL protein expression and promoted bone resorption, while up-regulation of miR-106b inhibited bone resorption. These results suggest that miR-106b is a novel suppressor of osteolysis by targeting RANKL and some other cytokines, which indicates that miR-106b may be a potential therapeutic target for the treatment of GCT.


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