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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

DTL is a Novel Downstream Gene of E2F1 that Promotes the Progression of Hepatocellular Carcinoma

Author(s): Ruiqiang Dong, Danhua Zhang, Baowei Han, Lingxue Xu, Danfeng Zhang, Zhenguo Cheng and Xinguang Qiu*

Volume 23, Issue 10, 2023

Published on: 01 June, 2023

Page: [817 - 828] Pages: 12

DOI: 10.2174/1568009623666230511100246

Price: $65

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.

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