Abstract
BackgroundOsteosarcoma (OS) is the most common bone malignancy prevalent in children and young adults. MicroRNA-133b (miR-133b), through directly targeting the fibroblast growth factor receptor 1 (FGFR1), is increasingly recognized as a tumor suppressor in different types of cancers. However, little is known on the biological and functional significance of miR-133b/FGFR1 regulation in osteosarcoma.MethodsThe expressions of miR-133b and FGFR1 were examined by RT-qPCR and compared between 30 paired normal bone tissues and OS tissues, and also between normal osteoblasts and three OS cells lines, MG-63, U2OS, and SAOS-2. Using U2OS and MG-63 as the model system, the functional significance of miR-133b and FGFR1 was assessed on cell viability, proliferation, apoptosis, migration/invasion, and epithelial–mesenchymal transition (EMT) by overexpressing miR-133b and down-regulating FGFR1 expression, respectively. Furthermore, the signaling cascades controlled by miR-133b/FGFR1 were examined.ResultsmiR-133b was significantly down-regulated while FGFR1 robustly up-regulated in OS tissues and OS cell lines, when compared to normal bone tissues and normal osteoblasts, respectively. Low miR-133b expression and high FGFR1 expression were associated with location of the malignant lesion, advanced clinical stage, and distant metastasis. FGFR1 was a direct target of miR-133b. Overexpressing miRNA-133b or knocking down FGFR1 significantly reduced the viability, proliferation, migration/invasion, and EMT, but promoted apoptosis of both MG-63 and U2OS cells. Both the Ras/MAPK and PI3K/Akt intracellular signaling cascades were inhibited in response to overexpressing miRNA-133b or knocking down FGFR1 in OS cells.ConclusionmiR-133b, by targeting FGFR1, presents a plethora of tumor suppressor activities in OS cells. Boosting miR-133b expression or reducing FGFR1 expression may benefit OS therapy.
Highlights
Osteosarcoma (OS) is the most common and a highly aggressive bone malignancy primarily developing in teenagers and young adults [1]
We showed that fibroblast growth factor receptor 1 (FGFR1) was a direct target gene inhibited by miR-133b in OS cells and their expressions were significantly correlated with location of the malignant lesion, higher staging or the presence of metastasis in OS patients
Results miR‐133b was down‐regulated while FGFR1 up‐regulated in OS tissues or cell lines Earlier studies reported the down-regulation of miR133b [10] and the up-regulation of FGFR1 [17] in OS, together with their clinical significance
Summary
Osteosarcoma (OS) is the most common and a highly aggressive bone malignancy primarily developing in teenagers and young adults [1]. MiRNAs act, either positively or negatively, on all the hallmarks of cancers, namely “sustaining proliferative signaling, evading growth suppression, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis” [6]. Recent studies revealed the tumor suppressor activities of miR-133b in different human cancers [9]. In OS, miR-133b expression was significantly reduced and re-introduction of miR-133b in osteosarcoma cells inhibited cell proliferation, induced apoptosis, and suppressed migration/ invasion [10]. Osteosarcoma (OS) is the most common bone malignancy prevalent in children and young adults. MicroRNA-133b (miR-133b), through directly targeting the fibroblast growth factor receptor 1 (FGFR1), is increasingly recognized as a tumor suppressor in different types of cancers. Little is known on the biological and func‐ tional significance of miR-133b/FGFR1 regulation in osteosarcoma
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