Unraveling the physiological roles of retinoic acid receptor-related orphan receptor α

Abstract

Retinoic acid receptor-related orphan receptor-α (RORα) is a member of the orphan nuclear receptor family and functions as a transcriptional activator in response to circadian changes. Circadian rhythms are complex cellular mechanisms regulating diverse metabolic, inflammatory, and tumorigenic gene expression pathways that govern cyclic cellular physiology. Disruption of circadian regulators, including RORα, plays a critical role in tumorigenesis and facilitates the development of inflammatory hallmarks. Although RORα contributes to overall fitness among anticancer, anti-inflammatory, lipid homeostasis, and circadian clock mechanisms, the molecular mechanisms underlying the mode of transcriptional regulation by RORα remain unclear. Nonetheless, RORα has important implications for pharmacological prevention of cancer, inflammation, and metabolic diseases, and understanding context-dependent RORα regulation will provide an innovative approach for unraveling the functional link between cancer metabolism and rhythm changes.

Cannabidiol Promotes Neuronal Differentiation Using Akt and Erk Pathways Triggered by Cb1 Signaling

“…Using the transcriptomics analysis, we study the correlation between the treatment of CBD the retinoic acid receptor-related orphan receptors (RORs). RORs are involved in the circadian rhythm [ 40 ], but also in neuronal differentiation [ 41 , 42 ]. Given the experimental nature of our work, it is difficult to think of a conventional activation of the circadian cycle, so we can say that ROR is used for neurodifferentiation.…”

Addition of losartan to FOLFORINOX and chemoradiation downregulates pro-invasion and immunosuppression-associated genes in locally advanced pancreatic cancer

“…4B). The retinoic acid receptor-related orphan receptor alpha (RORa) the protein product of RORA is involved in tumor suppression, and plays pro-and anti-inflammatory roles, which are context-dependent [30][31][32]. RORA in tumors treated with losartan+FFX+CRT correlated strongly with NFATC4 (Spearman R=0.918) a gene also upregulated by losartan+FFX+CRT (Supplementary Fig.…”

Nuclear Receptors (PPARs, REV-ERBs, RORs) and Clock Gene Rhythms in Goldfish (Carassius auratus) Are Differently Regulated in Hypothalamus and Liver

“…Nuclear receptors (NRs) belong to a superfamily of ligand-activated transcription factors that regulate gene transcription by modulating essential physiological processes such as growth, development, immunity, and metabolic homeostasis ( Kojetin and Burris, 2014 ; Ribas-Latre and Eckel-Mahan, 2016 ; Lee et al, 2021 ). All NRs described up to the present share a great homology in their amino acid sequence with highly conserved domain structures ( Solt et al, 2011 ).…”

“…However, there are also a huge number of other less known NRs recently described. Recent studies have advanced in the knowledge of three subfamilies of NRs participating as critical regulators of circadian clock, with significant roles in the regulation of metabolism ( Solt et al, 2011 ; Kojetin and Burris, 2014 ; Berthier et al, 2021 ; Lee et al, 2021 ). These three subfamilies are the nuclear receptor subfamily 1 group C ( nr1c ), commonly named as PPAR; the nuclear receptor subfamily 1 group D ( nr1d ) or REV-ERB, and the nuclear receptor subfamily 1 group F ( nr1f ) or retinoic acid-related orphan receptor (ROR) ( Nuclear Receptors Nomenclature Committee, 1999 ; Weikum et al, 2018 ).…”

“…As regulators of genes involved in lipid and glucose metabolism (lipid storage and lipogenesis, hepatic fatty acid oxidation, gluconeogenesis, or ketogenesis among several functions), these three subfamilies of proteins provide an essential key for the maintenance of energy homeostasis in metabolic tissues ( Chen and Yang, 2014 ; Pawlak et al, 2015 ; Vieira et al, 2015 ; Duszka and Wahli, 2020 ; Berthier et al, 2021 ; Lee et al, 2021 ). Although they were considered orphan receptors for a long time, different endogenous compounds have been emerged as natural ligands for these NRs.…”