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The miR-15b-5p/PDK4 axis regulates osteosarcoma proliferation through modulation of the Warburg effect.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 Sep 18; Vol. 503 (4), pp. 2749-2757. Date of Electronic Publication: 2018 Aug 06. - Publication Year :
- 2018
-
Abstract
- Blocking aerobic glycolysis has been proposed as an attractive therapeutic strategy for impairing the proliferation of cancer cells. However, the underlying mechanisms are poorly understood. Here, we show that miR-15b-5p was downregulated in osteosarcoma (OS) and that lower expression of miR-15b-5p promoted proliferation and contributed to the Warburg effect in OS cells. Mechanistically, miR-15b-5p acted as a tumor suppressor in OS by directly targeting pyruvate dehydrogenase kinase-4 and inhibiting its expression. These results reveal a previously unknown function of miR-15b-5p in OS, which is associated with metabolic alterations that promote cancer progression. miR-15b-5p may play an essential role in the molecular therapy of patients with OS.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- 3' Untranslated Regions
Animals
Apoptosis
Base Sequence
Binding Sites
Bone Neoplasms metabolism
Bone Neoplasms mortality
Bone Neoplasms pathology
Cell Line, Tumor
Cell Proliferation
Glycolysis genetics
Humans
Male
Mice
Mice, Nude
MicroRNAs metabolism
Osteoblasts pathology
Osteosarcoma metabolism
Osteosarcoma mortality
Osteosarcoma pathology
Protein Serine-Threonine Kinases antagonists & inhibitors
Protein Serine-Threonine Kinases metabolism
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
Survival Analysis
Xenograft Model Antitumor Assays
Bone Neoplasms genetics
Gene Expression Regulation, Neoplastic
MicroRNAs genetics
Osteoblasts metabolism
Osteosarcoma genetics
Protein Serine-Threonine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 503
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 30093112
- Full Text :
- https://doi.org/10.1016/j.bbrc.2018.08.035