Affiliation:
1. Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2. Department of General Surgery, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang, China
3. National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Abstract
Background:
Hepatocellular carcinoma (HCC), one of the world's most prevalent malignancies,
accounts for 90% of primary liver cancer cases. Recent studies have shown an increased expression
of denticles E3 ubiquitin protein ligase homolog (DTL) in several different tumor types, but
its function and regulatory mechanisms remain unclear.
Aims:
This study aimed to investigate the expressions of the Cullin4 (CUL4) complex in HCC and
elucidate the roles of DTL in HCC cells.
Methods:
The relative expression of the CUL4 complex and its clinical significance were analyzed
with The Cancer Genome Atlas (TCGA) data, and the level of DTL was confirmed by immunohistochemistry.
The functions of DTL1 and upstream E2F1 were evaluated by a Western blot, MTT,
transwell, and xenograft in HCC cell lines.
Results:
The elevated mRNA expression of the CUL4 complex, including CUL4B, DDB1 (Damage
Specific DNA Binding Protein 1), and DTL, was associated with the overall survival of HCC patients.
We also found that the DTL protein was elevated in HCC tissues, and patients with highly expressed
DTL and nucleus-located DTL had a poorer survival time. DTL knockdown significantly inhibited
cancer proliferation, migration, and invasion. Further experiments showed that E2F1 was an upstream
regulatory molecule of DTL, which was bound to the promoter of DTL, promoting the expression of
DTL.
Conclusion:
The study results demonstrate that E2F1-DTL signaling promotes the growth, migration,
and invasion of HCC cells, which provides new insights and a potential biological target for future
HCC therapies
Funder
Natural Science Foundation of Henan Province
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Drug Discovery,Pharmacology,Oncology
Cited by
1 articles.
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