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MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2.

Jiang B, Mu W, Wang J, Lu J, Jiang S, Li L, Xu H, Tian H - J. Exp. Clin. Cancer Res. (2016)

Bottom Line: MicroRNA-138 (miR-138) has been proven to be a tumor suppressor gene in various types of tumors.Moreover, miR-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues.DEC2 was verified as a direct target of miR-138, and DEC2 could reverse the inhibitory effect of miR-138 on osteosarcoma progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China. baoen_jiang@163.com.

ABSTRACT

Background: MicroRNA-138 (miR-138) has been proven to be a tumor suppressor gene in various types of tumors. However, the expression and the role of miR-138 in human osteosarcoma are still poorly understood. We investigated the function and the underlying mechanism of miR-138 in osteosarcoma.

Methods: The expression of miR-138 in human osteosarcoma tissues and cell lines was detected by real-time PCR analysis. The gain-of-function and loss-of-function experiments were performed on osteosarcoma cell lines to investigate the effects of miR-138 on osteosarcoma progression, and to determine whether differentiated embryonic chondrocyte gene 2 (DEC2) mediates these effects. Cell proliferation, apoptosis and invasion were assessed by MTT, flow cytometry and transwell-matrigel assays. Dual-luciferase reporter assay was used to identify whether DEC2 is a direct target of miR-138.

Results: MiR-138 was significantly downregulated in human osteosarcoma tissues and cell lines. Moreover, miR-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues. The in vitro gain-of-function and loss-of-function experiments demonstrated that miR-138 inhibited cell proliferation and invasion, and promoted cell apoptosis of human osteosarcoma cells. DEC2 was verified as a direct target of miR-138, and DEC2 could reverse the inhibitory effect of miR-138 on osteosarcoma progression.

Conclusions: These findings suggested that miR-138 acts as a tumor suppressor in osteosarcoma.miR-138 inhibited cell proliferation and invasion, as well as promoted cell apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of DEC2. MiR-138/DEC2 may be a novel therapeutic target in osteosarcoma.

No MeSH data available.


Related in: MedlinePlus

DEC2 suppression attenuated the effects of miR-138 inhibitor on osteosarcoma cells. a Relative DEC2 protein expression in MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA. Lane 1, miR-Ctrl + si-Ctrl; lane 2, Inhibitor + si-Ctrl; lane 3, Inhibitor + si-DEC2. b Cell viability c Cell apoptosis rate d Cell invasion of MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA.*P < 0.05 and #P < 0.01 compared with the miR-Ctrl + si-Ctrl; &P < 0.05 and @P < 0.01 compared with the Inhibitor + si-Ctrl
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Fig6: DEC2 suppression attenuated the effects of miR-138 inhibitor on osteosarcoma cells. a Relative DEC2 protein expression in MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA. Lane 1, miR-Ctrl + si-Ctrl; lane 2, Inhibitor + si-Ctrl; lane 3, Inhibitor + si-DEC2. b Cell viability c Cell apoptosis rate d Cell invasion of MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA.*P < 0.05 and #P < 0.01 compared with the miR-Ctrl + si-Ctrl; &P < 0.05 and @P < 0.01 compared with the Inhibitor + si-Ctrl

Mentions: To further illustrate whether miR-138 affects human osteosarcoma cell proliferation, apoptosis and invasion through DEC2, DEC2 overexpression plasmid was transfected into the U2OS cells in the presence of miR-138 mimic, whereas DEC2 siRNA was transfected into the MG-63 cells in the presence of miR-138 inhibitor. As shown in Figs. 5a and 6a,the expression of DEC2 protein was significantly increased in U2OS cells (0.30 ± 0.06 vs.0.70 ± 0.20, P < 0.05) but decreased in MG-63 cells (0.68 ± 0.10 vs.0.37 ± 0.07, P < 0.05).Fig 5


MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2.

Jiang B, Mu W, Wang J, Lu J, Jiang S, Li L, Xu H, Tian H - J. Exp. Clin. Cancer Res. (2016)

DEC2 suppression attenuated the effects of miR-138 inhibitor on osteosarcoma cells. a Relative DEC2 protein expression in MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA. Lane 1, miR-Ctrl + si-Ctrl; lane 2, Inhibitor + si-Ctrl; lane 3, Inhibitor + si-DEC2. b Cell viability c Cell apoptosis rate d Cell invasion of MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA.*P < 0.05 and #P < 0.01 compared with the miR-Ctrl + si-Ctrl; &P < 0.05 and @P < 0.01 compared with the Inhibitor + si-Ctrl
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837633&req=5

Fig6: DEC2 suppression attenuated the effects of miR-138 inhibitor on osteosarcoma cells. a Relative DEC2 protein expression in MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA. Lane 1, miR-Ctrl + si-Ctrl; lane 2, Inhibitor + si-Ctrl; lane 3, Inhibitor + si-DEC2. b Cell viability c Cell apoptosis rate d Cell invasion of MG-63 cells following transfection with the miR-138 inhibitor and DEC2 siRNA.*P < 0.05 and #P < 0.01 compared with the miR-Ctrl + si-Ctrl; &P < 0.05 and @P < 0.01 compared with the Inhibitor + si-Ctrl
Mentions: To further illustrate whether miR-138 affects human osteosarcoma cell proliferation, apoptosis and invasion through DEC2, DEC2 overexpression plasmid was transfected into the U2OS cells in the presence of miR-138 mimic, whereas DEC2 siRNA was transfected into the MG-63 cells in the presence of miR-138 inhibitor. As shown in Figs. 5a and 6a,the expression of DEC2 protein was significantly increased in U2OS cells (0.30 ± 0.06 vs.0.70 ± 0.20, P < 0.05) but decreased in MG-63 cells (0.68 ± 0.10 vs.0.37 ± 0.07, P < 0.05).Fig 5

Bottom Line: MicroRNA-138 (miR-138) has been proven to be a tumor suppressor gene in various types of tumors.Moreover, miR-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues.DEC2 was verified as a direct target of miR-138, and DEC2 could reverse the inhibitory effect of miR-138 on osteosarcoma progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China. baoen_jiang@163.com.

ABSTRACT

Background: MicroRNA-138 (miR-138) has been proven to be a tumor suppressor gene in various types of tumors. However, the expression and the role of miR-138 in human osteosarcoma are still poorly understood. We investigated the function and the underlying mechanism of miR-138 in osteosarcoma.

Methods: The expression of miR-138 in human osteosarcoma tissues and cell lines was detected by real-time PCR analysis. The gain-of-function and loss-of-function experiments were performed on osteosarcoma cell lines to investigate the effects of miR-138 on osteosarcoma progression, and to determine whether differentiated embryonic chondrocyte gene 2 (DEC2) mediates these effects. Cell proliferation, apoptosis and invasion were assessed by MTT, flow cytometry and transwell-matrigel assays. Dual-luciferase reporter assay was used to identify whether DEC2 is a direct target of miR-138.

Results: MiR-138 was significantly downregulated in human osteosarcoma tissues and cell lines. Moreover, miR-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues. The in vitro gain-of-function and loss-of-function experiments demonstrated that miR-138 inhibited cell proliferation and invasion, and promoted cell apoptosis of human osteosarcoma cells. DEC2 was verified as a direct target of miR-138, and DEC2 could reverse the inhibitory effect of miR-138 on osteosarcoma progression.

Conclusions: These findings suggested that miR-138 acts as a tumor suppressor in osteosarcoma.miR-138 inhibited cell proliferation and invasion, as well as promoted cell apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of DEC2. MiR-138/DEC2 may be a novel therapeutic target in osteosarcoma.

No MeSH data available.


Related in: MedlinePlus