Disease relevance of RORA

• RORA was previously shown to be involved in the cellular response to hypoxia and here we demonstrate changes in the amount of RORA message produced in cells exposed to a variety of different cellular stresses [1].
• RAR-related orphan receptor A isoform 1 (RORa1) is disrupted by a balanced translocation t(4;15)(q22.3;q21.3) associated with severe obesity [2].
• Role of the orphan nuclear receptor ROR alpha in the control of the metastatic behavior of androgen-independent prostate cancer cells [3].
• Retinoic acid-receptor-related orphan receptor (ROR) alpha is a nuclear receptor involved in many pathophysiological processes such as cerebellar ataxia, inflammation, atherosclerosis and angiogenesis [4].
• Interestingly, the activity of the Rora promoter was enhanced by hypoxia in HepG2 human hepatoma cells, and this effect was dependent on an HRE (hypoxia response element) spanning from -229 to -225 [4].

High impact information on RORA

• Intriguingly, disruption of filopodia formation by suppressing the expression of either Ror2 or filamin A inhibits Wnt5a-induced cell migration, indicating that Ror2-mediated filopodia formation is essential for Wnt5a-induced cell migration [5].
• The receptor tyrosine kinase Ror2 plays important roles in developmental morphogenesis [5].
• Ror2-mediated cell migration requires the extracellular cysteine-rich domain (CRD), which is the binding site for Wnt5a, and the cytoplasmic proline-rich domain (PRD) of Ror2 [5].
• In the present study the function of retinoic acid receptor-related orphan receptor (ROR) alpha in bone metabolism has been examined [6].
• ROR(alpha) (NR1F1) and Reverb(alpha) (NR1D1) are two members of this family whose biological functions are largely unknown [7].

Chemical compound and disease context of RORA

• Recently, the participation of nuclear signalling via estrogen as well as RZR/ROR receptors in oncostatic action of melatonin on the breast cancer has been widely discussed [8].
• The aim of present study was to investigate effects of melatonin, the selective ligand for nuclear RZR/ROR receptors - CGP 52608, and methotrexate on growth of murine 16/C breast cancer cells [8].

Biological context of RORA

• We have mapped the RORA gene by fluorescence in situ hybridization to human chromosome 15q21-q22 [9].
• In addition, RORA appears to play a critical role in responses to cellular stress, lending further support to the idea that the large CFS genes function as part of a highly conserved stress response network that is uniquely susceptible to genomic instability in cancer cells [1].
• Here, we report that a response element in the promoter of 5-lipoxygenase binds specifically RZR alpha and ROR alpha 1, but not ROR alpha 2 and alpha 3 [10].
• Furthermore, mutagenesis experiments indicate that ROR(alpha) regulates Reverb(alpha) transcription via a monomeric ROR response element located in the Reverb(alpha) gene promoter [7].
• The orphan nuclear receptor ROR alpha has been shown to be involved in the control of cell growth and differentiation [3].

Anatomical context of RORA

• Here, we analyzed the expression of the three members of the retinoid-like orphan receptor (ROR) nuclear receptor subfamily during adipocyte differentiation [11].
• We have shown that the thiazolidinedione derivative CGP 52608, the specific ROR alpha ligand and activator, reduces the ability of DU 145 cells to invade a reconstituted basement membrane (Matrigel) [3].
• In the present study we first demonstrate that hypoxia increases the amount of Rora transcripts in a wide panel of cell lines derived from diverse tissues [4].
• Filopodia formation mediated by receptor tyrosine kinase Ror2 is required for Wnt5a-induced cell migration [5].
• We show, using genetically different or manipulated cultured cells, that Ror2 is critical for Wnt5a-induced, but not Wnt3a-induced, cell migration [5].

Associations of RORA with chemical compounds

• Retinoic acid receptor-related orphan receptor-alpha (RORalpha) (NR1F1) is an orphan nuclear receptor with a potential role in metabolism [12].
• The two subtypes of retinoid Z receptor (RZR alpha and beta) and the three splicing variants of retinoid orphan receptor (ROR alpha 1, alpha 2, and alpha 3) form a subfamily within the superfamily of nuclear hormone receptors [10].
• We examined the effects of various tumor promoters on transcription mediated by several nuclear receptors (RAR, TR, and ROR) by using thymidine kinase promoter-based reporter systems [13].
• We have also achieved enhanced production of IL-2 and IL-6 using CGP 52608, a specific ligand of the putative nuclear melatonin receptor RZR/ROR, raising the possibility of direct effects of melatonin on gene regulation in both Th1 cells and monocytes [14].
• A high-resolution X-ray crystal structure of the retinoic acid receptor-related orphan receptor (RORalpha; NR1F1), which reveals a molecule of cholesterol within the ligand binding pocket, is a breakthrough in functional analysis of this orphan nuclear receptor [15].

Other interactions of RORA

• In this study, we demonstrate that the 730 kb retinoic acid receptor-related orphan receptor alpha (RORA) gene is derived from the middle of the FRA15A (15q22.2) CFS [1].
• Overexpression of HIF-1alpha increased the activity of the Rora promoter through the HRE [4].
• Taken together, our data reveal Rora as a new HIF-1 target gene [4].

References