Abstract
BackgroundOsteosarcoma (OS) is a primary malignant bone tumor with a high rate of metastasis and a short 5-year survival rate. MiR-363 was downregulated in a variety of tumors and played a role in suppressing tumors. However, the roles of miR-363 in osteosarcoma remain unknown; thus, the purpose of this study was to explore the functions of miR-363 in osteosarcoma.MethodsCCK-8 and transwell assays were performed to evaluate the proliferation, migration, and invasion abilities of MG63 cells. The epithelial-mesenchymal transition (EMT) and apoptosis-associated proteins were measured by using Western blot assay. Luciferase reporter assay was utilized to verify whether miR-363 directly bound to the 3′-UTR of NOB1 mRNA.ResultsMiR-363 was downregulated while NOB1 was upregulated in osteosarcoma clinical tissue specimens and cell lines as compared with the adjacent normal tissue specimens and normal cell line. The miR-363 is reversely correlated with the expression of NOB1 in osteosarcoma tissues. Overexpression of miR-363 suppressed the ability of cell migration, invasion, and EMT, whereas low expression of miR-363 promoted this ability. In addition, miR-363 inhibited osteosarcoma proliferation both in vitro and in vivo and inhibited the apoptosis in MG63 cells. Interference of NOB1 could inhibit the migration, invasion, and EMT of osteosarcoma cell line MG63. NOB1 was verified to be a direct target of miR-363 and its expression was mediated by miR-363. Re-expression of NOB1 could partially reverse the inhibitory effect of miR-363 on cell migration and invasion. In addition, low expression of miR-363 or overexpression of NOB1 predicted poor prognosis of osteosarcoma patients.ConclusionMiR-363 inhibited osteosarcoma the proliferation, migration, invasion, and EMT and induced the apoptosis by directly targeting NOB1 in MG63 cells. The newly identified miR-363/NOB1 axis provides novel insights into the pathogenesis of osteosarcoma.
Highlights
Osteosarcoma was a primary malignant bone tumor with morbidity of 4,000,000 annually [1]
Song et al have discovered that miR-363 acted as a tumor suppressor to inhibit cell growth and migration [12]
All the results demonstrated that low expression of NOB1 inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells, which were consistent with the results when miR-363 was overexpressed
Summary
Osteosarcoma was a primary malignant bone tumor with morbidity of 4,000,000 annually [1]. MiR-363 played a role in suppressing cancer in variety of tumors that include gastric cancer, papillary thyroid carcinoma, hepatocellular carcinoma, and lung adenocarcinoma [8,9,10,11]. Song et al have discovered that miR-363 acted as a tumor suppressor to inhibit cell growth and migration [12]. Wang et al demonstrated similar findings; miR-363 inhibited lung adenocarcinoma cell proliferation, colony formation, and tumor growth [13]. In osteosarcoma, there are little papers which study on metastasis of miR-363; we investigate whether miR-363 suppressed cell migration, invasion, and EMT in osteosarcoma. Osteosarcoma (OS) is a primary malignant bone tumor with a high rate of metastasis and a short 5year survival rate. The roles of miR-363 in osteosarcoma remain unknown; the purpose of this study was to explore the functions of miR-363 in osteosarcoma
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