MiR-216a-5p/Hexokinase 2 axis regulates uveal melanoma growth through modulation of Warburg effect

Biochemical and Biophysical Research Communications
Ying LiuYifei Huang

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 therapeut...Continue Reading

Citations

Apr 2, 2020·International Journal of Molecular Sciences·Giuseppina RoscignoGerolama Condorelli
Jul 17, 2020·OncoTargets and Therapy·Yi Fan LiWen Bin Wei
Aug 13, 2020·International Journal of Molecular Sciences·Karen AughtonSarah E Coupland
Aug 13, 2020·Cellular and Molecular Life Sciences : CMLS·Chun YangPierre Hardy
Nov 4, 2020·Technology in Cancer Research & Treatment·Manman YingHong Ning
May 6, 2021·International Journal of Molecular Sciences·Francesco CiscatoAndrea Rasola
May 10, 2021·Journal of Experimental & Clinical Cancer Research : CR·Simona D'AguannoAntonietta Moramarco
May 11, 2021·Frontiers in Oncology·Soudeh Ghafouri-FardMohammad Taheri
Apr 12, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhou SuJian Pei

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