SphK2 over-expression promotes osteosarcoma cell growth

Oncotarget. 2017 Nov 6;8(62):105525-105535. doi: 10.18632/oncotarget.22314. eCollection 2017 Dec 1.

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.

Keywords: microRNA-19a-3p; oncotarget; osteosarcoma; sphk2.