Abstract
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.
Highlights
Over the past decades, the prognosis of osteosarcoma (OS) has been significantly improved [1,2,3,4,5,6]
Real-time PCR (“Quantitatively real-time PCR (qRT-PCR)”) assay results showed that Sphingosine kinase 2 (SphK2) mRNA expression www.impactjournals.com/oncotarget in the OS tissues was significantly higher than that in the bone tissues (Figure 1A)
SphK2 protein was upregulated in OS tissues, and its expression was relative low in normal tissues (Figure 1B)
Summary
The prognosis of osteosarcoma (OS) has been significantly improved [1,2,3,4,5,6]. Production of pro-apoptotic sphingolipids, i.e. ceramide, will potently inhibit cancer cells. Anti-apoptotic sphingolipid sphingosine-1-phosphate (S1P) will promote cancer cell survival and growth [20,21,22]. The balance of these sphingolipids is tightly controlled by sphingosine kinase (SphK) [20]. Over-activation or upregulation of SphK would lead to increased conversion of ceramide to S1P, causing aberrant cell growth [20, 23]. Recent studies have proposed that SphK2 is over-expressed in many cancer cells [24,25,26]. Its expression and potential functions in human OS were tested in this study
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