RELA, also known as NF-κB p65, is a subunit of the nuclear factor kappa B (NF-κB) transcription factor complex. NF-κB signaling is involved in numerous biological processes, including immune response, inflammation, cell survival, and proliferation [3,4,5,6,7]. It plays a crucial role in regulating gene expression in response to various stimuli such as cytokines, oxidative stress, and pathogen-associated molecular patterns.

In silicosis, RELA-mediated upregulation of LINC03047 promotes ferroptosis and epithelial-mesenchymal transition (EMT) in silica-induced pulmonary fibrosis via SLC39A14, suggesting a potential new drug target for silicosis therapy [1]. In supratentorial ependymoma, the C11orf95-RELA fusion protein modulates chromatin states and mediates chromatin interactions, leading to transcriptional reprogramming in ependymoma cells, providing insights into potential therapeutic targets for this subtype of ependymoma [2]. In hypopharyngeal cancer, RELA is required for CD271 expression and stem-like characteristics, and inhibition of RELA binding to the CD271 promoter could be an effective therapeutic target [3]. In oral squamous cell carcinoma, RELA promotes the progression of the cancer via the TFAP2A-Wnt/β-catenin signaling pathway, and this pathway could be a potential target for reducing the aggressiveness of the cancer [4].

In conclusion, RELA is a key component of the NF-κB signaling pathway with significant functions in multiple biological processes and disease conditions. Through in vivo and in vitro studies, its role in diseases such as silicosis, ependymoma, hypopharyngeal cancer, and oral squamous cell carcinoma has been revealed, providing valuable insights into potential therapeutic strategies targeting RELA-related pathways.

References:

1. Zhang, Binbin, Wang, Enze, Zhou, Sijing, Cao, Chao, Wang, Ran. 2024. RELA-mediated upregulation of LINC03047 promotes ferroptosis in silica-induced pulmonary fibrosis via SLC39A14. In Free radical biology & medicine, 223, 250-262. doi:10.1016/j.freeradbiomed.2024.08.002. https://pubmed.ncbi.nlm.nih.gov/39111583/

2. Zhu, Jacqueline Jufen, Jillette, Nathaniel, Li, Xiao-Nan, Cheng, Albert Wu, Lau, Ching C. 2020. C11orf95-RELA reprograms 3D epigenome in supratentorial ependymoma. In Acta neuropathologica, 140, 951-960. doi:10.1007/s00401-020-02225-8. https://pubmed.ncbi.nlm.nih.gov/32909151/

3. Nakazato, Akira, Mochizuki, Mai, Shibuya-Takahashi, Rie, Asada, Yukinori, Tamai, Keiichi. 2022. RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer. In Scientific reports, 12, 17751. doi:10.1038/s41598-022-22736-6. https://pubmed.ncbi.nlm.nih.gov/36273237/

4. Yang, Kaicheng, Zhao, Jianguang, Liu, Shenghui, Man, Shasha. 2023. RELA promotes the progression of oral squamous cell carcinoma via TFAP2A-Wnt/β-catenin signaling. In Molecular carcinogenesis, 62, 641-651. doi:10.1002/mc.23512. https://pubmed.ncbi.nlm.nih.gov/36789977/

5. Zhang, Jie, Yu, Yuanyuan, Zou, Xiuqun, Chen, Lin-Feng, Yang, Xiao-Dong. . WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination. In Nucleic acids research, 52, 4969-4984. doi:10.1093/nar/gkae161. https://pubmed.ncbi.nlm.nih.gov/38452206/

6. Lu, Xinyuan, Yarbrough, Wendell G. 2014. Negative regulation of RelA phosphorylation: emerging players and their roles in cancer. In Cytokine & growth factor reviews, 26, 7-13. doi:10.1016/j.cytogfr.2014.09.003. https://pubmed.ncbi.nlm.nih.gov/25438737/

7. Geismann, Claudia, Hauser, Charlotte, Grohmann, Frauke, Schreiber, Stefan, Arlt, Alexander. 2023. NF-κB/RelA controlled A20 limits TRAIL-induced apoptosis in pancreatic cancer. In Cell death & disease, 14, 3. doi:10.1038/s41419-022-05535-9. https://pubmed.ncbi.nlm.nih.gov/36596765/