Abstract
BackgroundAberrant microRNA (miRNA) expression plays an essential role in osteosarcoma (OS) pathogenesis. Recent studies have shown that dysregulation of miRNA expression is associated with increased tumorigenesis and poor prognosis in several types of cancers, including OS. The aim of this study was to investigate the relevant microRNAs involved in the development of OS.MethodsTo explore possible oncogenic factors in OS, we used a microarray-based approach to profile changes in the expression of miRNAs and their target mRNAs in five OS cell lines and human mesenchymal stem cells (hMSCs). An miRNA, miR-93, was significantly up-regulated, whereas phosphatase and tensin homologue (PTEN) expression was significantly down-regulated in all tested OS cells, when compared with hMSCs.ResultsWhen anti-miR-93 was transfected into OS cell lines, PTEN expression was greatly increased, suggesting that PTEN might be a target of miR-93 in ES cells. The expression of phosphorylated Akt protein, which is known to be inversely correlated with that of PTEN, was significantly down-regulated in anti-miR-93-transfected cells. Furthermore, transfection of anti-miR-93 inhibited the proliferation and cell cycle progression of ES cells. In addition, the down-regulation of miR-93 in these cells significantly suppressed tumor growth in vivo.ConclusionEctopic expression of miR-93 decreased PTEN protein levels. Furthermore, miR-93 increased proliferation and decreased apoptosis in OS cells, whereas its silencing in these cells inhibited such carcinogenic processes. Taking these observations together, miR-93 can be seen to play a critical role in carcinogenesis through suppression of PTEN, and may serve as a therapeutic target for the treatment of OS.
Highlights
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents
Our results indicated that the expression of miR-93 was elevated while that of phosphatase and tensin homologue (PTEN) was repressed in all five OS cell lines, in comparison to human mesenchymal stem cells (hMSCs)
Our miRNA array results demonstrated that the expression of miR-93 was up-regulated in all five OS cell lines. miR-93 overexpression plays an important role in promoting lung cancer cell growth, angiogenesis, and metastasis, while its inhibition suppresses cell proliferation, migration, and colony formation [17, 18]
Summary
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators of gene expression in both cancer cells and normal cells. These noncoding small RNAs bind to specific cognate sequences in the 3′-untranslated region (3′-UTR) of target transcripts, MiR-93 expression has been implicated in various cancer types, implying an oncogenic role [5,6,7]. Its overexpression has been correlated with proliferation and tumor progression [8]. Aberrant microRNA (miRNA) expression plays an essential role in osteosarcoma (OS) pathogenesis. Recent studies have shown that dysregulation of miRNA expression is associated with increased tumorigenesis and poor prognosis in several types of cancers, including OS.
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