Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 503, Issue 2, Pages 459-466Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.04.124
Keywords
Osteosarcoma; miR-139-5p; DNMT1; Migration; Invasion
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Background: Accumulating evidence has suggested the crucial roles of differentially expressed miRNAs in osteosarcoma progression. MiR-139-5p was decreased in various cancers. However, the role of miR-139-5p in the development of osteosarcoma and the underlying mechanism remain to be addressed. Methods: MiR-139-5p and DNA methyltransferase-1 (DNMT1) mRNA expressions in osteosarcoma tissues and cells were detected by qRT-PCR and western blot analysis. The effects of miR-139-5p and DNMT1 on osteosarcoma cell migration, invasion and epithelial-mesenchymal transition (EMT) were investigated through cell migration and invasion assays, and western blot analysis. The relationship between miR-139-5p and DNMT1 was explored using luciferase reporter analysis and western blot. A xenograft tumor model was employed to verify the effects of miR-139-5p on osteosarcoma. Results: We found that miR-139-5p was strikingly decreased in osteosarcoma tissues and cell lines. MiR-139-5p over-expression suppressed osteosarcoma cell growth, migration and invasion, while loss of miR-139-5p promoted osteosarcoma cell proliferation, migration and invasion. Following, we characterized that DNMT1 was a direct target of miR-139-5p that interacted with the 3'-untranslated region of DNMT1. MiR-139-5p regulated a down-regulation in DNMT1 protein expression levels. We also found that DNMT1 expression was increased and negatively correlated with miR-139-5p expression in osteosarcoma tissues clinically. Xenograft tumor analysis suggested that miR-139-5p over-expression reduced tumor growth in osteosarcoma in vivo through decreasing DNMT1 expressions. Conclusion: MiR-139-5p suppressed the osteosarcoma progression by reducing DNMT1, supplying new insight into the molecular mechanism uncovering osteosarcoma growth. (C) 2018 Published by Elsevier Inc.
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