MicroRNA-127-3p inhibits proliferation and invasion by targeting SETD8 in human osteosarcoma cells.

MicroRNAs (miRNAs) play an essential role in cancer development. Several studies have indicated that miRNAs mediate tumorigenesis processes, such as, inflammation, proliferation, apoptosis and invasion. In the present study, we focused on the influence of the miR-127-3p on the proliferation, migration and invasion of osteosarcoma (OS). MiR-127-3p was found at reduced levels in OS tissues and cell lines. Overexpression of miR-127-3p in the OS cell lines significantly inhibited the cell proliferation, migration and invasion; however, inhibition of miR-127-3p increased the proliferation, migration and invasion of OS in vitro. SETD8 was identified as a direct target of miR-127-3p, and SETD8 expression decreased post miR-127-3p overexpression, while SETD8 overexpression could reverse the potential influence of miR-127-3p on the migration and invasion of OS cells. MiR-127-3p is suggested to act mainly via the suppression of SETD8 expression. Overall, the results revealed that miR-127-3p acts as a tumor suppressor and that its down-regulation in cancer may contribute to OS progression and metastasis, suggesting that miR-127-3p could be a potential therapeutic target in the treatment of OS.

Zhang J ，Hou W ，Chai M ，Zhao H ，Jia J ，Sun X ，Zhao B ，Wang R ... -  《-》

Loss of miR-217 promotes osteosarcoma cell proliferation through targeting SETD8.

Yang G ，Wang J ，Huang B 《-》

MicroRNA-185 inhibits proliferation, migration and invasion in human osteosarcoma MG63 cells by targeting vesicle-associated membrane protein 2.

MicroRNAs (miRNAs) play an essential role in cancer development. Several studies have indicated that miRNAs mediate tumorigenesis processes, such as inflammation, proliferation, apoptosis and invasion. In the present study, we aimed to investigate the role of the microRNA-185 (miR-185) on the proliferation, migration and invasion of osteosarcoma (OS). MiR-185 expression was reduced in OS tissues and OS cell lines. MiR-185 inhibited OS cell proliferation, migration and invasion. Furthermore, a dual-luciferase assay validated that vesicle-associated membrane protein 2 (VAMP2) was a direct target of miR-185. Overexpression of miR-185 in OC cells reduced VAMP2 expression in protein and mRNA levels, whereas suppression of miR-185 led to an increase in VAMP2 protein and mRNA levels. In addition, we found that VAMP2 silencing inhibited the OS cell proliferation, migration and invasion. Further studies verified that introducing VAMP2 mRNA into cells over-expressing miR-185 abrogated the effects of miR-185 on OS cell proliferation, migration and invasion. Therefore, these results confirm that decreased expression of miR-185 might be regarded as a tumor marker for the early diagnosis of OS, by manipulating of its interactive factors with VAMP2, to provide an effective novel therapeutic target for treatment of the OS tumor.

Li L ，Wang X ，Liu D 《-》

MicroRNA-384 downregulates SETD8 expression to suppress cell growth and metastasis in osteosarcoma cells.

Zhang JF ，Zhang GY ，Hu XM ，Luo ZP ，Ma YZ ... -  《-》

MicroRNA-338-3p inhibits tumor growth and metastasis in osteosarcoma cells by targeting RUNX2/CDK4 and inhibition of MAPK pathway.

Osteosarcoma (OS) is one of the most aggressive bone tumors. MicroRNAs (miRNAs) have been found to implicate in the pathogenesis of different types of cancers, including OS. This study aimed to explore the roles of miR-338-3p in OS and investigate the underlying mechanism. Human OS cell lines (MG-63 and U2OS) and osteoblast (hFOB) cell line were used in the study. The expression levels of miR-338-3p, runt-related transcription factor 2 (RUNX2) and cyclin-dependent kinase 4 (CDK4) were altered by transient transfection and determined by quantitative real-time polymerase chain reaction/Western blot analysis. Cell viability, colony numbers, migration, and invasion, and apoptotic cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, transwell assay, and flow cytometry assay, respectively. Dual luciferase reporter assay was performed to identify the target gene of miR-338-3p. Western blot assay was carried to measure the protein expression levels involved in cell apoptosis, migration, and mitogen-activated protein kinases (MAPK) pathway. We found that the expression of miR-338-3p was downregulated in MG-63 cell and U2OS cells, compared with hFOB cells. MiR-338-3p suppression significantly increased cell viability and colony numbers, promoted cell migration, and invasion, but suppressed cell apoptosis in MG-63 and U2OS cells. Opposite results were observed in the miR-338-3p overexpression. Interestingly, RUNX2 and CDK4 were direct target genes of miR-338-3p. RUNX2 inhibition shared a similar effect of miR-338-3p mimic on MG-63 cells. Furthermore, miR-338-3p inhibited the activation of MAPK pathway in MG-63 cells. To conclude, these findings suggested that miR-338-3p functioned as a tumor suppressor in OS cells by targeting RUNX2 and CDK4, as well as inhibition of the MAPK pathway.

Jia F ，Zhang Z ，Zhang X 《-》