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Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1

View Article: PubMed Central - PubMed

ABSTRACT

There is increasing evidence that microRNAs (miRs) are implicated in tumor development and progression; however, their specific roles in osteosarcoma are not well understood. The aim of the present study was to investigate the role of miR-506 in the pathogenesis of osteosarcoma. The expression levels of miR-506 and astrocyte elevated gene-1 (AEG-1) mRNA were detected using quantitative polymerase chain reaction, and the protein levels of AEG-1, β-catenin, c-myc and cyclin D1 were determined using western blot analysis. The effects of miR-506 and AEG-1 on cell viability, colony forming ability and apoptosis were assessed using MTT assay, colony formation assay, and flow cytometry, respectively. Lucifer reporter assays were used to demonstrate whether AEG-1 is a direct target of miR-506. The present study identified that miR-506 was downregulated in osteosarcoma tissues and cells. Overexpression of miR-506 suppressed the proliferation and induced apoptosis in osteosarcoma cells in vitro and inhibited tumor formation in vivo. Overexpression of miR-506 significantly inhibited the luciferase activity of AEG-1 with a wild-type 3′-untranslated region, providing clear evidence that AEG-1 was a direct and functional downstream target of miR-506. Similar to the overexpression of miR-506, downregulation of AEG-1 lead to an inhibitory effect on osteosarcoma in vitro. Furthermore, overexpression of miR-506 or downregulation of AEG-1 inhibited the Wnt/β-catenin signaling pathway, and inhibition of this pathway by β-catenin small interfering RNA or CGP049090, a small molecule inhibitor, suppressed cell proliferation and induced apoptosis in vitro. Overall, the present data indicated that miR-506 functions as a tumor suppressor by targeting AEG-1 in osteosarcoma via the regulation of the Wnt/β-catenin signaling pathway.

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miR-506 inhibited the growth of human osteosarcoma MG63 xenografts. (A and B) Overexpression of miR-506 decreased tumor (A) volumes and (B) weights compared with miR-control. **P<0.01 vs. miR-control. miR, microRNA.
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f5-ol-0-0-4827: miR-506 inhibited the growth of human osteosarcoma MG63 xenografts. (A and B) Overexpression of miR-506 decreased tumor (A) volumes and (B) weights compared with miR-control. **P<0.01 vs. miR-control. miR, microRNA.

Mentions: To investigate whether miR-506 has a role in a mouse model of osteosarcoma, MG63 cells stably overexpressing miR-506 or control-miR were injected subcutaneously into nude mice. The tumor volume was measured every 7 days. A total of 28 days following inoculation, mice were sacrificed and tumor weights were measured. Overexpression of miR-506 significantly inhibited the tumor growth of MG63 xenografts compared with the negative control group, since the average volume and weight of the miR-506-overexpressing tumors were notably decreased (P=0.0023 and P=0.0017, respectively; Fig. 5A and B). Therefore, miR-506 clearly attenuates osteosarcoma cell growth in vivo.


Overexpression of miR-506 suppresses proliferation and promotes apoptosis of osteosarcoma cells by targeting astrocyte elevated gene-1
miR-506 inhibited the growth of human osteosarcoma MG63 xenografts. (A and B) Overexpression of miR-506 decreased tumor (A) volumes and (B) weights compared with miR-control. **P<0.01 vs. miR-control. miR, microRNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998420&req=5

f5-ol-0-0-4827: miR-506 inhibited the growth of human osteosarcoma MG63 xenografts. (A and B) Overexpression of miR-506 decreased tumor (A) volumes and (B) weights compared with miR-control. **P<0.01 vs. miR-control. miR, microRNA.
Mentions: To investigate whether miR-506 has a role in a mouse model of osteosarcoma, MG63 cells stably overexpressing miR-506 or control-miR were injected subcutaneously into nude mice. The tumor volume was measured every 7 days. A total of 28 days following inoculation, mice were sacrificed and tumor weights were measured. Overexpression of miR-506 significantly inhibited the tumor growth of MG63 xenografts compared with the negative control group, since the average volume and weight of the miR-506-overexpressing tumors were notably decreased (P=0.0023 and P=0.0017, respectively; Fig. 5A and B). Therefore, miR-506 clearly attenuates osteosarcoma cell growth in vivo.

View Article: PubMed Central - PubMed

ABSTRACT

There is increasing evidence that microRNAs (miRs) are implicated in tumor development and progression; however, their specific roles in osteosarcoma are not well understood. The aim of the present study was to investigate the role of miR-506 in the pathogenesis of osteosarcoma. The expression levels of miR-506 and astrocyte elevated gene-1 (AEG-1) mRNA were detected using quantitative polymerase chain reaction, and the protein levels of AEG-1, &beta;-catenin, c-myc and cyclin D1 were determined using western blot analysis. The effects of miR-506 and AEG-1 on cell viability, colony forming ability and apoptosis were assessed using MTT assay, colony formation assay, and flow cytometry, respectively. Lucifer reporter assays were used to demonstrate whether AEG-1 is a direct target of miR-506. The present study identified that miR-506 was downregulated in osteosarcoma tissues and cells. Overexpression of miR-506 suppressed the proliferation and induced apoptosis in osteosarcoma cells in vitro and inhibited tumor formation in vivo. Overexpression of miR-506 significantly inhibited the luciferase activity of AEG-1 with a wild-type 3&prime;-untranslated region, providing clear evidence that AEG-1 was a direct and functional downstream target of miR-506. Similar to the overexpression of miR-506, downregulation of AEG-1 lead to an inhibitory effect on osteosarcoma in vitro. Furthermore, overexpression of miR-506 or downregulation of AEG-1 inhibited the Wnt/&beta;-catenin signaling pathway, and inhibition of this pathway by &beta;-catenin small interfering RNA or CGP049090, a small molecule inhibitor, suppressed cell proliferation and induced apoptosis in vitro. Overall, the present data indicated that miR-506 functions as a tumor suppressor by targeting AEG-1 in osteosarcoma via the regulation of the Wnt/&beta;-catenin signaling pathway.

No MeSH data available.


Related in: MedlinePlus