miR-885-5p Negatively Regulates Warburg Effect by Silencing Hexokinase 2 in Liver Cancer

Molecular Therapy. Nucleic Acids
Fei XuQiu Zhao

Abstract

Growing tumor cells possess a distinct metabolic phenomenon that allows them to preferentially utilize glucose through aerobic glycolysis, which is referred to as the "Warburg effect." Accumulating evidence suggests that microRNAs (miRNAs) could regulate such metabolic reprogramming. Our microarray analysis and quantitative real-time PCR validation revealed that miR-885-5p was strongly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. To investigate miR-885-5p's biological functions in HCC progression, malignant phenotypes were analyzed in different types of hypoxic model and indicated that overexpression of miR-885-5p significantly inhibited HCC cell proliferation and migration and induced apoptosis in vitro and tumor growth in vivo. Subsequent investigations of whether miR-885-5p regulated the glycometabolic activity of cancer cells demonstrated that forced expression of miR-885-5p in SMMC-7721 cells significantly reduced glucose uptake and lactate production by repressing several key enzymes related to glycolysis. Particularly, miR-885-5p directly targets the 3' UTR of hexokinase 2 (HK2), which is a key enzyme that catalyzes the irreversible first step of glycolysis and associates with poor patient outc...Continue Reading

Citations

Nov 20, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Wenwu DuYi He
Jun 4, 2020·Cancer Cell International·Meng ShaoXu Zhang
Jul 8, 2020·Journal of Experimental & Clinical Cancer Research : CR·Jiao FengChuanyong Guo
Jan 13, 2021·Cancer Cell International·Jixin ShouHaibo Guan
May 21, 2021·Journal of Hepatocellular Carcinoma·Laura GramantieriFrancesca Fornari
Jun 26, 2021·Cellular Oncology (Dordrecht)·Yuting WangLin Miao
Aug 28, 2021·Cells·Ho-Yeop LeeHyon-Seung Yi
Mar 3, 2022·Clinical Science·Carlos J Pirola, Silvia Sookoian

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Datasets Mentioned

BETA
GSE20077

Methods Mentioned

BETA
PCR
flow cytometry
flow
transfection
Xenograft
biopsies
transfections
Assay

Software Mentioned

GraphPad
TargetScan
FACSDiva

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