Rarb-KO Mouse

Rarb, short for retinoic acid receptor beta, is a transcriptional regulator that plays a crucial role in coordinating retinoic acid (RA)-mediated morphogenic movements, cell growth, and differentiation [4]. It is involved in the retinoic acid signaling pathway, which is essential for numerous biological processes, including eye development, hematopoiesis, and neural development [4,5,6].

In gastric cancer, knockdown of Rarb accelerated the proliferation, invasion, and migration of cancer cells in vitro, promoting the epithelial-mesenchymal transition process. However, RARBLow patients had better survival compared to RARBHigh patients, and RARB expression was inversely correlated with MSI status and immune infiltrates in vivo [1].

In acute promyelocytic leukemia (APL), the majority of RARA-negative APL cases had RARB translocations. The TBL1XR1-RARB fusion protein homodimerized, diminished transcriptional activity of the retinoic acid receptor pathway, enhanced the replating capacity of mouse bone marrow cells, and inhibited myeloid maturation of human cord blood cells. APL with RARB translocation was less responsive to retinoids compared to PML-RARA positive cases [2].

In colorectal carcinoma, overexpression of RARB inhibited the properties of cancer stem cells and enhanced radiotherapy sensitivity. The methylation of RARB was higher in cancer stem cells, and inhibition of DNA methyltransferase 1 could improve radiotherapy sensitivity by promoting RARB expression [3].

In a case of complex microphthalmia, a de novo noncoding RARB variant was found to potentially promote RARB overexpression in human lens epithelial cells, leading to increased cell proliferation and elevated expression of a downstream target [4].

In conclusion, Rarb is essential for multiple biological processes through its role in the retinoic acid signaling pathway. Studies, including those using gene-knockout models in relevant disease areas such as cancer and leukemia, have revealed its significance in disease progression, prognosis, and response to treatment. Understanding Rarb can potentially provide new therapeutic targets for these diseases.

References:

1. Cai, Xufan, Lin, Wenfa, Wu, Fang, Qian, Zhenyuan, Wang, Yu. 2024. RARB associated with MSI, affects progression and prognosis of gastric cancer. In BMC gastroenterology, 24, 285. doi:10.1186/s12876-024-03339-z. https://pubmed.ncbi.nlm.nih.gov/39179979/

2. Osumi, Tomoo, Tsujimoto, Shin-Ichi, Tamura, Moe, Goyama, Susumu, Kato, Motohiro. 2018. Recurrent RARB Translocations in Acute Promyelocytic Leukemia Lacking RARA Translocation. In Cancer research, 78, 4452-4458. doi:10.1158/0008-5472.CAN-18-0840. https://pubmed.ncbi.nlm.nih.gov/29921692/

3. Shu, Yuxian, Lan, Jun, Hu, Zhaobing, Liu, Weiguo, Song, Rongfeng. . Epigenetic regulation of RARB overcomes the radio-resistance of colorectal carcinoma cells via cancer stem cells. In Journal of radiation research, 64, 11-23. doi:10.1093/jrr/rrac060. https://pubmed.ncbi.nlm.nih.gov/36214504/

4. Replogle, Maria R, Thompson, Samuel, Reis, Linda M, Semina, Elena V. 2024. A De Novo Noncoding RARB Variant Associated with Complex Microphthalmia Alters a Putative Regulatory Element. In Human mutation, 2024, . doi:10.1155/2024/6619280. https://pubmed.ncbi.nlm.nih.gov/39450403/

5. Schönberger, Katharina, Obier, Nadine, Romero-Mulero, Mari Carmen, Pearce, Erika L, Cabezas-Wallscheid, Nina. 2021. Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity. In Cell stem cell, 29, 131-148.e10. doi:10.1016/j.stem.2021.10.002. https://pubmed.ncbi.nlm.nih.gov/34706256/

6. Shibata, Mikihito, Pattabiraman, Kartik, Lorente-Galdos, Belen, Sousa, Andre M M, Sestan, Nenad. 2021. Regulation of prefrontal patterning and connectivity by retinoic acid. In Nature, 598, 483-488. doi:10.1038/s41586-021-03953-x. https://pubmed.ncbi.nlm.nih.gov/34599305/