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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

Authors :
Nan Du
Yan Huo
Wei Zhao
Dajiang Wang
Dongbo Pang
Yanhong Tai
Yifei Huang
Yan Zhang
Ying Liu
Jie Li
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.

Details

ISSN :
10902104
Volume :
501
Issue :
4
Database :
OpenAIRE
Journal :
Biochemical and biophysical research communications
Accession number :
edsair.doi.dedup.....4e4d7fbca27b52bef7409c84da26b935