Related Experiment Video
Updated: Jul 26, 2025
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
WDR74 serves as a novel therapeutic target by its oncogenic role in hepatocellular carcinoma
Feng Gao1, Hui Zhou2, Xiaosong Huang3
1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, China; NHC Key Laboratory of Combined Multi-organ Transplantation, China; Key Laboratory of the diagnosis and treatment of organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences (2019RU019), China; Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Zhejiang Province, Hangzhou 310003, China.
Background:
Hepatocellular carcinoma (HCC) is one of the most refractory human malignancies. WD repeat-containing protein 74 (WDR74) is involved in the tumorigenesis of various cancers, however, its clinical implications and biological function in HCC have yet to be clearly determined.
Methods:
Bioinformatics analysis was conducted using various databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN. The expression of WDR74 was confirmed in HCC tumor samples and the corresponding adjacent nontumor samples by qRT-PCR, western blot and immunohistochemistry. Functional enrichment analysis was used for the biological function prediction. In vitro experiments were performed to determine the effects of WDR74 on HCC cell proliferation.
Results:
Our findings revealed that WDR74 was markedly upregulated in HCC tissues. Increased WDR74 expression had an unfavorable overall survival (OS). Multivariate Cox regression analysis demonstrated that WDR74 was an independent prognostic factor for OS in patients with HCC. Functional enrichment analysis suggested a significant correlation with cytokine-cytokine receptor interaction pathway in both TCGA-LIHC and GSE112790 datasets. Gene set enrichment analysis showed that WDR74 is probably involved in several pathways, such as MYC targets, ribosome, translation, and cell cycle. Finally, WDR74 knockdown reduced HCC cell proliferation by restraining the G1/S cell cycle transition and inducing apoptosis.
Conclusions:
The current study demonstrates that elevated WDR74 expression is linked to an accelerated rate of tumor cell proliferation and is indicative of a poorer outcome in patients with HCC. Therefore, WDR74 could be used as a reliable prognostic biomarker and is a potential therapeutic target for HCC.
Insights
WD repeat-containing protein 74 (WDR74) is upregulated in hepatocellular carcinoma (HCC), correlating with poor survival. Targeting WDR74 may inhibit HCC cell proliferation and offer a new therapeutic strategy for this refractory cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) remains a challenging malignancy.
- The role of WD repeat-containing protein 74 (WDR74) in HCC tumorigenesis is not well understood.
Purpose of the Study:
- To investigate the clinical significance and biological function of WDR74 in HCC.
- To evaluate WDR74 as a prognostic biomarker and potential therapeutic target for HCC.
Main Methods:
- Bioinformatic analysis using TCGA, GEO, and UALCAN databases.
- Expression analysis via qRT-PCR, western blot, and immunohistochemistry.
- In vitro experiments assessing WDR74's impact on HCC cell proliferation and cell cycle.
Main Results:
- WDR74 expression is significantly elevated in HCC tissues.
- Higher WDR74 levels correlate with unfavorable overall survival (OS) in HCC patients.
- WDR74 knockdown inhibits HCC cell proliferation by affecting cell cycle progression and inducing apoptosis.
Conclusions:
- Elevated WDR74 expression is a prognostic indicator for poor outcomes in HCC.
- WDR74 is implicated in HCC cell proliferation and represents a potential therapeutic target.
Related Concept Videos
02:54Canonical Wnt Signaling Pathway
01:41Non-Canonical Wnt Signaling Pathways
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:23Abnormal Proliferation
02:38Mitogens and the Cell Cycle
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...