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Published on: July 22, 2020
Systems-level analysis of gene expression data revealed NR0B2/SHP as potential tumor suppressor in human liver cancer
Yun-Yong Park1, Hueng-Sik Choi, Ju-Seog Lee
1Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. yypark@mdanderson.org
Abstract:
Nuclear receptors (NRs) play pivotal roles in cell growth, proliferation, differentiation and homeostasis. Recent progress demonstrates that NR is tightly linked to human disease such as cancer, diabetes and obesity. Here we explore NR expression profiles in human tissue using systematic approaches. NR gene profiles reveal that individual NR has its own gene expression signature depending on tissue type. Of many organs, NRs expression is enriched in liver. Expression of many NRs was significantly changed in liver cancer. Notably, NR0B2/SHP expression level was significantly decreased in human liver cancer but not in normal liver. In addition, expression of SHP is well associated with good prognosis. SHP gene network analysis based on microarray data in liver cancer shows that SHP regulates cell proliferation and metabolism related gene sets. Our systematic approaches suggest that loss of SHP expression in liver might be key genetic events during hepatocarcinogenesis.
Insights
Nuclear receptors (NRs) are crucial for cell functions and linked to diseases like cancer. Loss of NR0B2/SHP expression in liver cancer correlates with poor prognosis and altered cell proliferation and metabolism.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Nuclear receptors (NRs) are critical regulators of cellular processes including growth, differentiation, and homeostasis.
- Dysregulation of NRs is implicated in various human diseases, notably cancer, diabetes, and obesity.
- Understanding NR expression patterns in different tissues is essential for elucidating their roles in health and disease.
Purpose of the Study:
- To systematically investigate nuclear receptor expression profiles across human tissues.
- To identify specific NR expression changes associated with liver cancer.
- To explore the functional significance of NR0B2/SHP in hepatocarcinogenesis.
Main Methods:
- Systematic analysis of nuclear receptor gene expression profiles in human tissues.
- Microarray data analysis to assess NR expression in liver cancer.
- Gene network analysis to identify SHP-regulated pathways in liver cancer.
Main Results:
- Individual nuclear receptors exhibit distinct tissue-specific gene expression signatures.
- NR expression is notably enriched in the liver, with significant alterations observed in liver cancer.
- NR0B2/SHP expression is significantly decreased in human liver cancer, inversely correlating with prognosis and regulating cell proliferation and metabolism genes.
Conclusions:
- Loss of NR0B2/SHP expression represents a potential key genetic event in liver cancer development.
- SHP plays a critical role in regulating cellular proliferation and metabolism within the liver.
- Targeting SHP or its regulatory pathways may offer therapeutic strategies for liver cancer.
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