Rras, a gene encoding a small monomeric GTPase, plays a crucial role in controlling cell adhesion, spreading, and migration [6]. It is involved in the RAS/mitogen-activated protein kinase pathway, which is significant in cell cycle regulation [4,6]. Dysregulation of Rras has implications for various biological processes and disease development.

In a study on pulmonary fibrosis, endothelial-specific Foxf1 inhibition in mice increased collagen depositions, promoted lung inflammation, and impaired R-Ras signaling. FOXF1 was found to inhibit TNFα and CCL2 through direct transcriptional activation of the Rras gene promoter. Transgenic overexpression or endothelial-specific nanoparticle delivery of Foxf1 cDNA decreased pulmonary fibrosis in bleomycin-injured mice, suggesting Rras is involved in the regulation of pulmonary fibrosis by lung endothelial cells [1]. In nasopharyngeal carcinoma, the expression of RRAS was down-regulated and associated with poor prognosis. RRAS suppressed proliferation, invasion, and epithelial-mesenchymal transformation of related cell lines, indicating it may act as a tumor suppressor gene [5]. In biliary atresia, the expression of RRAS was negatively correlated with the elimination rate of jaundice and positively correlated with the occurrence rate of cholangitis, suggesting it is an important regulatory module in the pathogenesis and a potential prognostic marker [2]. In bladder cancer, the METTL3/YTHDF2 m6A axis promotes malignant progression by epigenetically suppressing RRAS [3]. Also, germline mutations in RRAS have been associated with pediatric myelodysplastic syndrome and juvenile myelomonocytic leukemia, expanding the phenotype of RASopathies [4,6].

In conclusion, Rras is essential for cell adhesion, spreading, and migration, and is involved in key pathways like RAS/mitogen-activated protein kinase. Model-based research, especially in mouse models, has revealed its significant roles in diseases such as pulmonary fibrosis, nasopharyngeal carcinoma, biliary atresia, bladder cancer, and hematological malignancies. Understanding Rras provides insights into disease mechanisms and potential therapeutic targets in these disease areas.

References:

1. Bian, Fenghua, Lan, Ying-Wei, Zhao, Shuyang, Kalinichenko, Vladimir V, Kalin, Tanya V. 2023. Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling. In Nature communications, 14, 2560. doi:10.1038/s41467-023-38177-2. https://pubmed.ncbi.nlm.nih.gov/37137915/

2. Zhao, Rui, Li, Hao, Shen, Chun, Zheng, Shan. . RRAS: A key regulator and an important prognostic biomarker in biliary atresia. In World journal of gastroenterology, 17, 796-803. doi:10.3748/wjg.v17.i6.796. https://pubmed.ncbi.nlm.nih.gov/21390152/

3. Chen, Jie-Xun, Chen, Dong-Ming, Wang, Dong, Zhu, Shuai, Xu, Xian-Lin. 2023. METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS. In Oncology reports, 49, . doi:10.3892/or.2023.8531. https://pubmed.ncbi.nlm.nih.gov/36960869/

4. Catts, Daniel S, Mroske, Cameron, Clark, Rebecca O, Hunter, Jesse M, Whiteway, Susan L. . Pediatric Myelodysplastic Syndrome With Germline RRAS Mutation: Expanding the Phenotype of RASopathies. In Journal of pediatric hematology/oncology, 43, e517-e520. doi:10.1097/MPH.0000000000001910. https://pubmed.ncbi.nlm.nih.gov/32815881/

5. Xiao, Ruowen, Shi, Lu, Yang, Te, Wang, Huiyun, Mai, Shijuan. . Identification of RRAS gene related to nasopharyngeal carcinoma based on pathway and network-based analyses. In Translational cancer research, 8, 664-675. doi:10.21037/tcr.2019.04.04. https://pubmed.ncbi.nlm.nih.gov/35116799/

6. Flex, Elisabetta, Jaiswal, Mamta, Pantaleoni, Francesca, Ahmadian, Mohammad R, Tartaglia, Marco. 2014. Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis. In Human molecular genetics, 23, 4315-27. doi:10.1093/hmg/ddu148. https://pubmed.ncbi.nlm.nih.gov/24705357/