RARRES1 Human

RARRES1 is located on chromosome 3q25 and is adjacent to the Latexin (LXN) gene . The gene is known to produce multiple transcript variants encoding distinct isoforms . The protein encoded by RARRES1 is involved in various cellular processes, including the regulation of fatty acid metabolism and the alpha-tubulin tyrosination cycle .

The expression of RARRES1 is upregulated by retinoic acid receptors and tazarotene, a topical retinoid used in the treatment of psoriasis and acne . However, the expression of this gene is found to be downregulated in several cancers, including prostate cancer, due to the methylation of its promoter and CpG island .

RARRES1 has been identified as a tumor suppressor and plays a significant role in metabolic reprogramming of epithelial cells . It regulates fatty acid metabolism by inhibiting the cytoplasmic carboxypeptidase AGBL2, which may influence the alpha-tubulin tyrosination cycle . In epithelial cells, depletion of RARRES1 leads to an increase in lipid synthesis and a switch from aerobic glycolysis to glucose-dependent de novo lipogenesis (DNL) . This metabolic shift provides an advantage to cells during starvation by increasing fatty acid availability for mitochondrial respiration .

RARRES1 is differentially expressed in various metabolic diseases, such as hepatic steatosis, hyperinsulinemia, and obesity . Its expression is also contextually correlated with the expression of fatty acid metabolism genes and fatty acid-regulated transcription factors . The gene’s hypermethylation and subsequent loss of expression have been observed in multiple cancers, making it a potential target for cancer therapy .

The role of RARRES1 in regulating fatty acid metabolism and its tumor suppressor function opens up new avenues for research and therapeutic interventions. Targeting RARRES1 and its associated pathways could provide novel strategies for treating cancers and metabolic diseases with impaired fatty acid metabolism .