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MiR-216a-5p/Hexokinase 2 axis regulates uveal melanoma growth through modulation of Warburg effect
MiR-216a-5p/Hexokinase 2 axis regulates uveal melanoma growth through modulation of Warburg effect
- Source :
- Biochemical and biophysical research communications. 501(4)
- Publication Year :
- 2018
-
Abstract
- Hexokinase-2 (HK2), the initial as well as the rate-limiting step in glycolysis, is overexpressed in many human cancers, and correlates with poor clinical outcomes. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its enzymes, including HK2, are being developed. However, the mechanisms of HK2 inhibition and the physiological significance of the HK2 inhibitors in cancer cells are rarely reported . Here, we show that microRNA-216a-5p (miR-216a-5p) inhibits HK2 expression by directly targeting its 3′-UTR in uveal melanoma cells. Through inhibition of HK2, miR-216a-5p dampens glycolysis by reducing HK activity, glucose uptake, lactate production, ATP generation, extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in uveal melanoma cells. Importantly, glycolysis regulated by miR-216a-5p is critical for its regulating uveal melanoma tumor growth both in vitro and in vivo. miR-216a-5p expression is negatively correlated with HK2 expression and predicts better outcome in uveal melanoma patients. Our findings provide clues regarding the role of miR-216a-5p as a tumor suppressor in uveal melanoma through the inhibition of HK2. Targeting HK2 through miR-216a-5p could be a promising therapeutic strategy in uveal melanoma.
- Subjects :
- 0301 basic medicine
Uveal Neoplasms
Glucose uptake
Biophysics
Biochemistry
law.invention
03 medical and health sciences
Mice
0302 clinical medicine
law
Cell Line, Tumor
Hexokinase
medicine
Animals
Humans
Glycolysis
Molecular Biology
Melanoma
Cell Proliferation
Base Sequence
Chemistry
Cancer
Cell Biology
medicine.disease
Prognosis
Warburg effect
Aerobiosis
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
HEK293 Cells
Anaerobic glycolysis
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Suppressor
Signal Transduction
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 501
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....4e4d7fbca27b52bef7409c84da26b935