Retinoic Acid Receptor-Related Orphan Receptors: Critical Roles in Tumorigenesis

Abstract

Retinoic acid receptor-related orphan receptors (RORs) include RORα (NR1F1), RORβ (NR1F2), and RORγ (NR1F3). These receptors are reported to activate transcription through ligand-dependent interactions with co-regulators and are involved in the development of secondary lymphoid tissues, autoimmune diseases, inflammatory diseases, the circadian rhythm, and metabolism homeostasis. Researches on RORs contributing to cancer-related processes have been growing, and they provide evidence that RORs are likely to be considered as potential therapeutic targets in many cancers. RORα has been identified as a potential therapeutic target for breast cancer and has been investigated in melanoma, colorectal colon cancer, and gastric cancer. RORβ is mainly expressed in the central nervous system, but it has also been studied in pharyngeal cancer, uterine leiomyosarcoma, and colorectal cancer, in addition to neuroblastoma, and recent studies suggest that RORγ is involved in various cancers, including lymphoma, melanoma, and lung cancer. Some studies found RORγ to be upregulated in cancer tissues compared with normal tissues, while others indicated the opposite results. With respect to the mechanisms of RORs in cancer, previous studies on the regulatory mechanisms of RORs in cancer were mostly focused on immune cells and cytokines, but lately there have been investigations concentrating on RORs themselves. Thus, this review summarizes reports on the regulation of RORs in cancer and highlights potential therapeutic targets in cancer.

The effect of RORa expression on the development of biological malignancy of urinary bladder cancer

“…A literature review reveals that RORa is a widely distributed nuclear receptor known for its regulatory activity regarding metabolism, inflammation, angiogenesis or [17,31]. Increasingly, retinoid acid receptor-related orphan receptors are being studied in the context of cancer-related processes including gastric cancer, melanoma or colorectal cancer [32]. Fu RD et al observed that a lowered RORa expression was associated with worse survival prognosis in hepatocellular carcinoma [13].…”

Natural products as modulators of retinoic acid receptor-related orphan receptors (RORs)

“…45 Several types of cancer are linked to an increase or decrease in the activity of all three RORs (reviewed in ref. 46) as well. In short, RORa showed tumor suppressive activities that were amongst others mediated by p53 (ref.…”

“…RORg and especially its isoform RORgt are the most researched RORs due to their connection to various inammatory and autoimmune diseases such as multiple sclerosis, 51 rheumatoid arthritis (RA), 52 systemic lupus erythematosus (SLE), 53 psoriasis, 54,55 asthma, 56,57 and, again, cancer 46,58,59 (also reviewed in ref. 60).…”

Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing

“…Another patient displayed a RICTOR-CCDC152 fusion (Figure 5C and D). A fusion transcript RORA-LHFP composed of RORA exon 1 fused to LHFP exon 3 is shown in Figure 5E and F. The three fusion genes are speculated to be involved in tumor growth, as their partners have important roles in malignant diseases (24)(25)(26).…”

“…Gene fusions provide important clues for targeted therapy (26). In UPS, the data on fusion gene-guided therapy are limited.…”