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Updated: Nov 16, 2025

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
Published on: September 28, 2017
Research on the circadian clock gene HNF4a in different malignant tumors
Meng-Jun Qiu1, Li Zhang1, Xie-Fan Fang2
1Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China.
Abstract:
Background: The circadian rhythm is produced by multiple feedback loops formed by the core clock genes after transcription and translation, thus regulating various metabolic and physiological functions of the human body. We have shown previously that the abnormal expression of 14 clock genes is related closely to the occurrence and development of different malignant tumors, and these genes may play an anti-cancer or pro-cancer role in different tumors. HNF4a has many typical properties of clock proteins involved in the clock gene negative feedback loop regulation process. We need to explore the function of HNF4a as a circadian clock gene in malignant tumors further. Methods: We used The Cancer Genome Atlas (TCGA) database to download the clinicopathological information of twenty malignant tumors and the corresponding RNA-seq data. The HNF4a RNA-seq data standardized by R language and clinical information were integrated to reveal the relationship between HNF4a and prognosis of patients. Results: Analysis of TCGA data showed that the prognosis of HNF4a was significantly different in BLCA, KIRC, LUSC, and READ. High HNF4a expression is correlated with good prognosis in BLCA, KIRC, and READ but poor prognosis in LUSC. However, HNF4a was associated with the stages, T stages, and lymph node status only in BLCA. Conclusions: HNF4a plays different roles in different malignancies, and the abnormal expression of HNF4a has a great correlation with the biological characteristics of BLCA. The low expression of HNF4a could be a reference index for the metastasis, recurrence, and prognosis of BLCA.
Insights
Hepatocyte nuclear factor 4-alpha (HNF4a) exhibits varied roles in cancer. While high HNF4a expression correlates with better prognosis in several cancers, it indicates a poor prognosis in lung squamous cell carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Chronobiology
Background:
- Circadian rhythm, regulated by core clock genes, influences human metabolism and physiology.
- Aberrant expression of clock genes is linked to various cancers, acting as either pro-cancer or anti-cancer factors.
- Hepatocyte nuclear factor 4-alpha (HNF4a) possesses characteristics of clock proteins involved in negative feedback loops.
Purpose of the Study:
- To investigate the function of HNF4a as a circadian clock gene in malignant tumors.
- To explore the prognostic significance of HNF4a across different cancer types.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database for RNA-sequencing and clinical data from twenty malignant tumors.
- Integrated standardized HNF4a RNA-seq data with clinicopathological information to analyze patient prognosis.
Main Results:
- HNF4a expression significantly impacts prognosis in bladder cancer (BLCA), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), and rectal adenocarcinoma (READ).
- High HNF4a expression correlates with favorable prognosis in BLCA, KIRC, and READ, but with poor prognosis in LUSC.
- HNF4a is associated with tumor stage, T stage, and lymph node status specifically in BLCA.
Conclusions:
- HNF4a demonstrates differential roles across various malignancies.
- Aberrant HNF4a expression is closely linked to the biological characteristics of BLCA.
- Low HNF4a expression may serve as a prognostic biomarker for metastasis, recurrence, and overall outcome in BLCA.
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