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Fructose-Bisphosphate Aldolase A Regulates Hypoxic Adaptation in Hepatocellular Carcinoma and Involved with Tumor Malignancy.

Abstract：

BACKGROUND:Hypoxia is an important factor in malignant tumors, and glycolysis is a major metabolic contributor in their development. Glycolytic enzymes have gained increasing attention as potential therapeutic targets because they are associated with cancer-specific metabolism. Fructose-bisphosphate aldolase A (ALDOA), a key glycolytic enzyme, reportedly is associated with hepatocellular carcinoma (HCC). However, its role in pathogenesis and its clinical significance in HCC remain largely unknown. AIM:To explore the increased expression of ALDOA in HCC in correlation with tumor malignancy, and to investigate the potential regulatory role ALDOA plays in HCC progression through its regulation in hypoxia adaptation. METHODS AND RESULTS:To better understand ALDOA and its correlation with clinicopathological features of HCC, we analyzed 100 HCC clinical specimens using immunohistochemistry analysis. The results show that the ALDOA expression level is significantly higher in advanced HCC and in HCC with venous invasion. Using in vitro knockdown assays, we showed that higher ALDOA expression was positively associated with cell proliferation, cell cycle, apoptosis, and invasion under both normoxic and hypoxic conditions. Evidence shows that the underlying mechanism is due to the regulatory function of ALDOA in glycolysis, the cell cycle, matrix metalloproteinase-mediated extracellular matrix degradation, and epithelial-mesenchymal transformation. CONCLUSIONS:Data indicated that ALDOA is significantly upregulated in HCC tissue and is closely related to HCC malignancy. ALDOA is likely to regulate HCC progression by regulating HCC tumor cell proliferation, apoptosis, and invasion in both normoxic and hypoxic condition.

journal_name

Dig Dis Sci

journal_title

Digestive diseases and sciences

authors

Li X,Jiang F,Ge Z,Chen B,Yu J,Xin M,Wang J,An L,Wei J,Wu L

doi

10.1007/s10620-019-05642-2

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

3215-3227

issue

eissn

0163-2116

issn

1573-2568

pii

10.1007/s10620-019-05642-2

journal_volume

pub_type

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Fructose-Bisphosphate Aldolase A Regulates Hypoxic Adaptation in Hepatocellular Carcinoma and Involved with Tumor Malignancy.