Abstract |
MicroRNA-370 (miR-370) has been observed to act as a tumor suppressor through the targeting of different proteins in a variety of tumors. Our previous study indicated that miR-370 was able to target forkhead box protein M1 (FOXM1) to inhibit cell growth and metastasis in human osteosarcoma cells. In this study, we reported that FOXM1 interacted with β- catenin in vitro and in vivo. Similar to FOXM1, critical components of the Wnt signaling pathway, including β- catenin, c-Myc, and Cyclin D1, were also highly expressed in different human osteosarcoma cells lines. Pharmacological inhibition of FOXM1 or β- catenin but not of c-Myc was associated with the increased expression of miR-370. Ectopic expression of miR-370 inhibited the downstream signaling of β- catenin. Moreover, osteosarcoma cells treated with 5-AZA-2'-deoxycytidine (AZA), a DNA methylation inhibitor, exhibited increased levels of miR-370 and decreased levels of β- catenin downstream targets, which resulted in inhibition of cell proliferation and colony formation ability. In conclusion, our results supported a model in which the DNA methylation-mediated down-regulation of miR-370 reduced its inhibitory effect on FOXM1, thereby promoting FOXM1-β-catenin interaction and activating the Wnt/β- Catenin signaling pathway in human osteosarcoma cells.
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Authors | Wentao Zhang, Ning Duan, Qian Zhang, Tao Song, Zhong Li, Caiguo Zhang, Xun Chen, Kunzheng Wang |
Journal | International journal of biological sciences
(Int J Biol Sci)
Vol. 13
Issue 5
Pg. 561-573
( 2017)
ISSN: 1449-2288 [Electronic] Australia |
PMID | 28539830
(Publication Type: Journal Article)
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Chemical References |
- Forkhead Box Protein M1
- MIRN370 microRNA, human
- MicroRNAs
- beta Catenin
- Cyclin D1
- Decitabine
- Azacitidine
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Topics |
- Azacitidine
(analogs & derivatives, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(genetics, physiology)
- Cyclin D1
(metabolism)
- DNA Methylation
(drug effects, genetics)
- Decitabine
- Forkhead Box Protein M1
(genetics, metabolism)
- Humans
- MicroRNAs
(genetics)
- Wnt Signaling Pathway
(genetics, physiology)
- beta Catenin
(metabolism)
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