The DNMT1miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells
Joint Authors
Liang, Xiao
Xu, Chang
Wang, Wanchun
Li, Xiang
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-10-31
Country of Publication
Egypt
No. of Pages
20
Abstract EN
The DNA methyltransferase 1 (DNMT1)/miR-34a axis promoted carcinogenesis of various types of cancers.
However, no literature reported its contribution to the stemness of osteosarcoma cancer stem-like cells (OSLCs).
We sought to determine whether the DNMT1/miR-34a axis facilitates the stemness of OSLCs.
We here revealed the higher DNMT1 activity and expression, lower miR-34a expression with high methylation of its promoter, and stronger stemness of OSLCs, as manifested by elevated sphere and colony formation capacities; CD133, CD44, ABCG2, Bmi1, Sox2, and Oct4 protein amounts in vitro; and carcinogenicity in a nude mouse xenograft model, when compared to the parental U2OS cells.
5-Azacytidine (Aza-dC) repressed DNMT1 activation and upregulated miR-34a expression by promoter demethylation and suppressed the stemness of OSLCs in a dose-dependent manner.
DNMT1 knockdown increased miR-34a and reduced the stemness of OSLCs.
Transfection with a miR-34a mimic repressed the stemness of OSLCs but did not alter DNMT1 activity and expression.
Conversely, DNMT1 overexpression declined miR-34a levels, promoting the stemness of U2OS cells.
Transfection with a miR-34a inhibitor enhanced the stemness of U2OS cells, without affecting the DNMT1 activity and expression.
Importantly, reexpression of miR-34a could rescue the effects of DNMT1 overexpression on miR-34a inhibition as well as the stemness promotion without affecting the activity and expression of DNMT1.
Our results revealed that aberrant activation of DNMT1 caused promoter methylation of miR-34a, leading to miR-34a underexpression, and the role of the DNMT1/miR-34a axis in promoting and sustaining the stemness of OSLCs.
American Psychological Association (APA)
Liang, Xiao& Xu, Chang& Wang, Wanchun& Li, Xiang. 2019. The DNMT1miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells. Stem Cells International،Vol. 2019, no. 2019, pp.1-20.
https://search.emarefa.net/detail/BIM-1209431
Modern Language Association (MLA)
Liang, Xiao…[et al.]. The DNMT1miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells. Stem Cells International No. 2019 (2019), pp.1-20.
https://search.emarefa.net/detail/BIM-1209431
American Medical Association (AMA)
Liang, Xiao& Xu, Chang& Wang, Wanchun& Li, Xiang. The DNMT1miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells. Stem Cells International. 2019. Vol. 2019, no. 2019, pp.1-20.
https://search.emarefa.net/detail/BIM-1209431
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1209431