Rnd1, belonging to the Rho GTPase family, is an atypical Rho GTPase predominantly in an active GTP-bound conformation. It is involved in multiple biological functions. In healthy tissues, it has various roles, and in the context of disease, it is associated with pathways like the AKT/GSK3-β pathway, p53 signaling pathway, and Ras signaling pathway, and is important in processes such as cell adhesion, proliferation, invasion, and immunity [2].

In glioblastoma, overexpression of Rnd1 suppresses cell migration, epithelial-mesenchymal transition (EMT), and enhances temozolomide sensitivity via inhibiting the phosphorylation of AKT and GSK3-β [1]. In hepatocellular carcinoma, reduced Rnd1 expression, affected by promoter methylation, is associated with cancer progression and poor prognosis, likely through regulating the Ras signaling pathway [8]. In lung squamous cell carcinoma, low Rnd1 expression is related to cell proliferation, cisplatin resistance, and miR-4652-5p can target Rnd1 to promote tumor progression [5,9]. However, in esophageal squamous cell carcinoma, Rnd1 is up-regulated and promotes cell growth and migration by activating ERK signaling [7]. Also, Rnd1 defends against viral and bacterial infections in an interferon-independent manner, and in rheumatoid arthritis, its up-regulation inhibits synoviocyte proliferation, migration, invasion, and the inflammatory response via ferroptosis [3,4]. In cardiomyocytes, Rnd1 is a stretch-sensitive gene influencing cell proliferation and hypertrophy [6].

In summary, Rnd1 has diverse functions in different biological processes and diseases. Studies on Rnd1, including those using gene knockout or conditional knockout models (not explicitly detailed in provided references but potentially valuable), have revealed its significance in cancer, immunity, and cardiac remodeling. Understanding Rnd1 can offer insights into disease mechanisms and potential therapeutic targets.

References:

1. Sun, Qian, Xu, Junjie, Yuan, Fan'en, Dong, Huimin, Liu, Baohui. 2024. RND1 inhibits epithelial-mesenchymal transition and temozolomide resistance of glioblastoma via AKT/GSK3-β pathway. In Cancer biology & therapy, 25, 2321770. doi:10.1080/15384047.2024.2321770. https://pubmed.ncbi.nlm.nih.gov/38444223/

2. Mouly, Laetitia, Gilhodes, Julia, Lemarié, Anthony, Sordet, Olivier, Monferran, Sylvie. 2019. The RND1 Small GTPase: Main Functions and Emerging Role in Oncogenesis. In International journal of molecular sciences, 20, . doi:10.3390/ijms20153612. https://pubmed.ncbi.nlm.nih.gov/31344837/

3. Kumar, Akhilesh, Mishra, Shalabh, Kumar, Ashish, Takaoka, Akinori, Kumar, Himanshu. 2022. Essential role of Rnd1 in innate immunity during viral and bacterial infections. In Cell death & disease, 13, 520. doi:10.1038/s41419-022-04954-y. https://pubmed.ncbi.nlm.nih.gov/35654795/

4. Chen, Qiuhua, Chen, Donglan, Wang, Sijie, Xie, Tong, Lu, Jie. 2025. RND1 Induces Ferroptosis to Alleviate Inflammatory Response, Proliferation, Invasion, and Migration of Rheumatoid Synoviocytes. In Journal of inflammation research, 18, 2647-2659. doi:10.2147/JIR.S500630. https://pubmed.ncbi.nlm.nih.gov/40008082/

5. Zhou, Yafu, Yan, Jianhua, Chen, Huiguo, Zou, Haoyu, Yang, Jinsong. 2022. MiR-4652-5p Targets RND1 to Regulate Cell Adhesion and Promote Lung Squamous Cell Carcinoma Progression. In Applied biochemistry and biotechnology, 194, 3031-3043. doi:10.1007/s12010-022-03897-6. https://pubmed.ncbi.nlm.nih.gov/35334070/

6. Kluge, Annika, Rangrez, Ashraf Yusuf, Kilian, Lucia Sophie, Frey, Norbert, Frank, Derk. 2019. Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy. In Journal of molecular and cellular cardiology, 129, 130-143. doi:10.1016/j.yjmcc.2019.01.028. https://pubmed.ncbi.nlm.nih.gov/30797814/

7. Xiang, Guo, Yi, Yang, Weiwei, He, Weiming, Wu. 2015. RND1 is up-regulated in esophageal squamous cell carcinoma and promotes the growth and migration of cancer cells. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 773-9. doi:10.1007/s13277-015-3855-7. https://pubmed.ncbi.nlm.nih.gov/26250459/

8. Komatsu, Hisateru, Iguchi, Tomohiro, Masuda, Takaaki, Mori, Masaki, Mimori, Koshi. 2016. Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma. In Annals of surgical oncology, 24, 850-859. doi:10.1245/s10434-016-5573-9. https://pubmed.ncbi.nlm.nih.gov/27770342/

9. Zhou, Yafu, Chen, Huiguo, Yan, Jianhua, Xiao, Shengying, Yang, Jinsong. . FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma. In The clinical respiratory journal, 18, e13814. doi:10.1111/crj.13814. https://pubmed.ncbi.nlm.nih.gov/39129202/