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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Research

A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors

Authors: Luqiao Wang, Gayani Nanayakkara, Qian Yang, Hongmei Tan, Charles Drummer, Yu Sun, Ying Shao, Hangfei Fu, Ramon Cueto, Huimin Shan, Teodoro Bottiglieri, Ya-feng Li, Candice Johnson, William Y. Yang, Fan Yang, Yanjie Xu, Hang Xi, Weiqing Liu, Jun Yu, Eric T. Choi, Xiaoshu Cheng, Hong Wang, Xiaofeng Yang

Published in: Journal of Hematology & Oncology | Issue 1/2017

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Abstract

Background

Nuclear receptors (NRs) can regulate gene expression; therefore, they are classified as transcription factors. Despite the extensive research carried out on NRs, still several issues including (1) the expression profile of NRs in human tissues, (2) how the NR expression is modulated during atherosclerosis and metabolic diseases, and (3) the overview of the role of NRs in inflammatory conditions are not fully understood.

Methods

To determine whether and how the expression of NRs are regulated in physiological/pathological conditions, we took an experimental database analysis to determine expression of all 48 known NRs in 21 human and 17 murine tissues as well as in pathological conditions.

Results

We made the following significant findings: (1) NRs are differentially expressed in tissues, which may be under regulation by oxygen sensors, angiogenesis pathway, stem cell master regulators, inflammasomes, and tissue hypo-/hypermethylation indexes; (2) NR sequence mutations are associated with increased risks for development of cancers and metabolic, cardiovascular, and autoimmune diseases; (3) NRs have less tendency to be upregulated than downregulated in cancers, and autoimmune and metabolic diseases, which may be regulated by inflammation pathways and mitochondrial energy enzymes; and (4) the innate immune sensor inflammasome/caspase-1 pathway regulates the expression of most NRs.

Conclusions

Based on our findings, we propose a new paradigm that most nuclear receptors are anti-inflammatory homeostasis-associated molecular pattern receptors (HAMPRs). Our results have provided a novel insight on NRs as therapeutic targets in metabolic diseases, inflammations, and malignancies.
Appendix
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Metadata
Title
A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors
Authors
Luqiao Wang
Gayani Nanayakkara
Qian Yang
Hongmei Tan
Charles Drummer
Yu Sun
Ying Shao
Hangfei Fu
Ramon Cueto
Huimin Shan
Teodoro Bottiglieri
Ya-feng Li
Candice Johnson
William Y. Yang
Fan Yang
Yanjie Xu
Hang Xi
Weiqing Liu
Jun Yu
Eric T. Choi
Xiaoshu Cheng
Hong Wang
Xiaofeng Yang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0526-8

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