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Background: Hepatocellular carcinoma (HCC) is characterized by high vascularity and notable abnormality of blood vessels, where angiogenesis is a key process in tumorigenesis and metastasis. The main functions of Nei Like DNA Glycosylase 3 (NEIL3) include DNA alcoholization repair, immune response regulation, nervous system development and function, and DNA damage signal transduction. However, the underlying mechanism of high expression NEIL3 in the development and progression of HCC and whether the absence or silencing of NEIL3 inhibits the development of cancer remain unclear. Therefore, a deeper understanding of the mechanisms by which increased NEIL3 expression promotes cancer development is needed., Methods: Expression of NEIL3 and its upstream transcription factor MAZ in HCC tumor tissues was analyzed in bioinformatics efforts, while validation was done by qRT-PCR and western blot in HCC cell lines. The migration and tube formation capacity of HUVEC cells were analyzed by Transwell and tube formation assays. Glycolytic capacity was analyzed by extracellular acidification rate, glucose uptake, and lactate production levels. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter gene assays were utilized to investigate specific interactions between MAZ and NEIL3., Results: NEIL3 and MAZ were substantially upregulated in HCC tissues and cells. NEIL3 was involved in modulating the glycolysis pathway, suppression of which reversed the stimulative impact of NEIL3 overexpression on migration and angiogenesis in HUVEC cells. MAZ bound to the promoter of NEIL3 to facilitate NEIL3 transcription. Silencing MAZ reduced NEIL3 expression and suppressed the glycolysis pathway, HUVEC cell migration, and angiogenesis., Conclusion: MAZ potentiated the upregulated NEIL3-mediated glycolysis pathway and HCC angiogenesis. This study provided a rationale for the MAZ/NEIL3/glycolysis pathway as a possible option for anti-angiogenesis therapy in HCC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with a poor prognosis. Aspartate β-hydroxylase (ASPH) is an α-ketoglutarate-dependent dioxygenase involved in the post-translational hydroxylation of target proteins. ASPH has been demonstrated to be upregulated in ICC, yet its role remains to be elucidated. This study aimed to investigate the potential function of ASPH in ICC metastasis., Methods: Survival curves for the overall survival of pan-cancer data from The Cancer Genome Atlas (TCGA) database was depicted using the Kaplan-Meier method and compared using the log-rank test. The expression of ASPH, glycogen synthase kinase (GSK)-3β, phosphorylation GSK-3β (p-GSK-3β), epithelial-mesenchymal transition (EMT) biomarkers, and sonic hedgehog (SHH) signaling elements in ICC cell lines was analyzed by western blot. Wound healing and transwell assays were conducted to examine the effects of ASPH knockdown and overexpression on cell migration and invasion. An immunofluorescence assay was conducted to evaluate the expression of glioma-associated oncogene 2 (GLI2), GSK-3β and ASPH. The effect of ASPH on tumor in vivo was analyzed using a nude mouse xenograft model., Results: Pan-cancer data showed that expressed ASPH was significantly correlated with a poor prognosis in patients. ASPH knockdown inhibited the migration and invasion of human ICC cells lines QBC939 and RBE. ASPH overexpression contributed to an increase in the N-cadherin and Vimentin, resulting in the promotion of the EMT process. The p-GSK-3β levels decreased in the presence of ASPH overexpression. The overexpression of ASPH led to an upregulation of the expression of SHH signaling elements GLI2 and SUFU. The results of in vivo experiments with a lung metastasis model in nude mice with ICC cell line RBE are consistent with these results., Conclusion: ASPH accelerated metastasis of ICC cells by facilitating EMT via a GSK-3β/SHH/GLI2 axis-dependent manner, in which phosphorylation of GSK-3β was downregulated and the SHH signaling pathway was activated., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)