Title:Transcription Factor MAZ Potentiates the Upregulated NEIL3-mediated Aerobic Glycolysis, thereby Promoting Angiogenesis in Hepatocellular Carcinoma
Volume: 24
Issue: 12
关键词:
NEIL3，血管生成，糖酵解信号通路，MAZ，肝细胞癌。
摘要:
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.
