کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8292473 | 1536732 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
MiR-216a-5p/Hexokinase 2 axis regulates uveal melanoma growth through modulation of Warburg effect
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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![عکس صفحه اول مقاله: 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](/preview/png/8292473.png)
چکیده انگلیسی
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 3â²-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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 501, Issue 4, 2 July 2018, Pages 885-892
Journal: Biochemical and Biophysical Research Communications - Volume 501, Issue 4, 2 July 2018, Pages 885-892
نویسندگان
Ying Liu, Yan Huo, Dajiang Wang, Yanhong Tai, Jie Li, Dongbo Pang, Yan Zhang, Wei Zhao, Nan Du, Yifei Huang,