SphK2 over-expression promotes osteosarcoma cell growth
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Dawei Xu1,*, Hao Zhu2,*, Chengniu Wang3, Wei Zhao1, Genxiang Liu2, Guofeng Bao1, Daoran Cui1, Jianbo Fan1, Fei Wang1, Huricha Jin1 and Zhiming Cui1
1Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong, China
2Department of Orthopaedics, The Fourth Affiliated Hospital of Nantong University, Yancheng, China
3Basic Medical Research Centre, Medical College, Nantong University, Nantong, China
*These authors have contributed equally to this work
Zhiming Cui, email: [email protected]
Keywords: osteosarcoma; sphk2; microRNA-19a-3p; oncotarget
Received: May 30, 2017 Accepted: July 13, 2017 Published: November 06, 2017
It is needed to explore novel biological markers for early diagnosis and treatment of human osteosarcoma. Sphingosine kinase 2 (SphK2) expression and potential functions in osteosarcoma were studied. We demonstrate that SphK2 is over-expressed in multiple human osteosarcoma tissues and established human osteosarcoma cell lines. Silence of SphK2 by targeted-shRNAs inhibited osteosarcoma cell growth, and induced cell apoptosis. On the other hand, exogenous over-expression of SphK2 could further promote osteosarcoma cell growth. Notably, microRNA-19a-3p (“miR-19a-3p”) targets the 3’ UTR (untranslated region) of SphK2 mRNA. Remarkably, forced-expression of miR-19a-3p silenced SphK2 and inhibited osteosarcoma cell growth. In vivo, SphK2 silence, by targeted-shRNA or miR-19a-3p, inhibited U2OS tumor growth in nude mice. These results suggest that SphK2 could be a novel and key oncotarget protein for OS cell progression.
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