MicroRNA-124 upregulation inhibits proliferation and invasion of osteosarcoma cells by targeting sphingosine kinase 1

Abstract

Increasing evidence has confirmed that the dysregulation of microRNAs (miRNAs) contributes to the proliferation and invasion of human cancers. Previous studies have shown that the dysregulation of miR-124 is in numerous cancers. However, the roles of miR-124 in human osteosarcoma (OS) have not been well clarified. Therefore, this study was to investigate the biological functions and molecular mechanisms of miR-124 in OS cell lines, discussing whether it could be a therapeutic biomarker of OS in the future. In this study, our results demonstrated that miR-124 was down-regulated in OS cell lines and tissues. Furthermore, the low level of miR-124 was associated with increased expression of Sphingosine kinase 1 (SPHK1) in OS cells and tissues. Up-regulation of miR-124 significantly inhibited cell proliferation, invasion, and MMP-2 and -9 expressions of OS cells. Bioinformatics analysis predicted that the SPHK1 was a potential target of miR-124. Further study by luciferase reporter assay demonstrated that miR-124 could directly target SPHK1. Overexpression of SPHK1 in OS cells transfected with miR-124 mimic partially reversed the inhibitory of miR-124. In conclusion, miR-124 inhibited cell proliferation and invasion in OS cells by downregulation of SPHK1, and that downregulation of SPHK1 was essential for the miR-124-inhibited cell invasion and in OS cells.

Sphingosine Kinase 1 and Sphingosine-1-Phosphate Signaling in Colorectal Cancer

“…Several lines of evidence have also demonstrated that Sphk1 is a downstream target of microRNAs and acts as oncogene in promoting tumorigenesis and progression. For example, miRNA-124 has been shown downregulated in various types of solid cancers, and acts as a tumor suppressor by inhibiting cancer cell proliferation, invasion, and metastasis in the head and neck squamous cell carcinoma, osteosarcoma, ovarian, and gastric cancers by targeting Sphk1 signaling [ 27 , 28 , 29 ]. MiRNA-101 inhibited colorectal cancer cell proliferation by targeting Sphk1 [ 30 ].…”

Advances in the role of miRNAs in the occurrence and development of osteosarcoma

“…The study of drugs affects the expression level of miRNAs in OS cells, which in turn affects the progression and prognosis of tumors, and provides a new direction for the study of molecular targeted drugs for the treatment of OS [43][44][45][46]. However, although there is a deep understanding of the differential expression and functional roles of some miRNAs in OS, there are still many difficulties to overcome in order to treat OS through the targeting of miRNAs: the sequence error of the miRNA sequence library, poor RNA extraction methods, variability in detection and analysis, diversity of bioinformatics analysis, and non-standardization of miRNA clinical tests [47,48]. In conclusion, the exploration of the relationship between miRNAs and OS provides new ideas and challenges for the early diagnosis, molecular targeted therapy, and prognosis of OS [49][50][51].…”

What Is New in the miRNA World Regarding Osteosarcoma and Chondrosarcoma?

“…Their study demonstrated that overexpression of miR-409-3p reduced OS cell migration and invasion and that this effect was mediated by targeting catenin-δ1, which has been described as an oncogene via aberrant regulation of Rho GTPases and the transcriptional activation of other oncogenes [ 235 ]. Within the last year, two groups have studied miR-124 in OS [ 236 , 237 ]; the first demonstrated that upregulation of miR-124, which is often downregulated in OS cells, blocks proliferation and invasion by targeting the SPHK1 gene. SPHK1 has been reported to be involved in several cellular processes including cancer metastasis.…”

“…SPHK1 has been reported to be involved in several cellular processes including cancer metastasis. Hence, Zhou et al have described for the first time an association between miR-124 and SPHK1 [ 236 ]. The other group showed the tumour suppressor activity of miR124 and demonstrated that this activity is related to targeting B7-H3, a protein that promotes uncontrollable proliferation and invasion [ 237 ].…”