RASSF2, short for Ras association domain family member 2, is a tumor suppressor gene. It contains Ras association and SARAH domains and is involved in multiple biological processes. RASSF2 binds to K-Ras in a GTP-dependent manner and is thought to function as a scaffolding protein, modulating the activity of pro-apoptotic effectors, thus regulating tumor suppressor pathways [4,8,9]. It is associated with pathways such as the Hippo pathway through interaction with Hippo kinases MST1 and MST2, and also with Rac GTPase signaling [5].

In various diseases, RASSF2 has been extensively studied. In gastric cancer, RASSF2 methylation was significantly higher in cancer tissues compared to adjacent non-tumor tissues, suggesting it could predict the risk of gastric cancer, though not tumor metastasis [1]. In Ewing sarcoma, RASSF2 methylation was frequent, and it correlated with poor overall survival, especially in patients under 18 years old [6]. In squamous cervical cancer, RASSF2 hypermethylation was predominant, associated with lower expression, vascular invasion, and shorter survival [7]. In age-related cataract, RASSF2 was identified as an effector gene of epigallocatechin gallate (EGCG), with high RASSF2 expression playing a crucial role in oxidative induction of apoptosis in lens epithelial cells [2]. Additionally, in abdominal aortic aneurysm, hyperhomocysteinemia may aggravate its formation by up-regulating RASSF2 [3].

In conclusion, RASSF2 is a significant tumor suppressor gene involved in multiple disease conditions. Its methylation status is often associated with cancer prognosis, and its expression is involved in non-cancerous diseases like age-related cataract and abdominal aortic aneurysm. The study of RASSF2 provides insights into the mechanisms of these diseases, potentially offering new strategies for diagnosis, prognosis, and treatment.

References:

1. Zhou, Kena, Cai, Congbo, He, Yi, Ding, Xiaoyun, Duan, Shiwei. 2019. Association Between RASSF2 Methylation and Gastric Cancer: A PRISMA-Compliant Systematic Review and Meta-Analysis. In DNA and cell biology, 38, 1147-1154. doi:10.1089/dna.2019.4922. https://pubmed.ncbi.nlm.nih.gov/31453724/

2. Liu, Shanhe, Su, Dongmei, Sun, Zhaoyi, Ma, Xu, Hu, Shanshan. 2023. Epigallocatechin gallate delays age-related cataract development via the RASSF2/AKT pathway. In European journal of pharmacology, 961, 176204. doi:10.1016/j.ejphar.2023.176204. https://pubmed.ncbi.nlm.nih.gov/37979829/

3. Liu, Zongwei, Feng, Guilin, Chen, Yonghui, Bi, Jiaxue, Dai, Xiangchen. 2023. Hyperhomocysteinemia may aggravate abdominal aortic aneurysm formation by up-regulating RASSF2. In Gene, 898, 148036. doi:10.1016/j.gene.2023.148036. https://pubmed.ncbi.nlm.nih.gov/38036076/

4. Cooper, W N, Hesson, L B, Matallanas, D, Kolch, W, Latif, F. 2009. RASSF2 associates with and stabilizes the proapoptotic kinase MST2. In Oncogene, 28, 2988-98. doi:10.1038/onc.2009.152. https://pubmed.ncbi.nlm.nih.gov/19525978/

5. Stoner, Samuel A, Liu, Katherine Tin Heng, Andrews, Elizabeth T, Carter, Hannah, Zhang, Dong-Er. 2020. The RUNX1-ETO target gene RASSF2 suppresses t(8;21) AML development and regulates Rac GTPase signaling. In Blood cancer journal, 10, 16. doi:10.1038/s41408-020-0282-9. https://pubmed.ncbi.nlm.nih.gov/32029705/

6. Gharanei, Seley, Brini, Anna T, Vaiyapuri, Sumathi, Maher, Eamonn R, Latif, Farida. 2013. RASSF2 methylation is a strong prognostic marker in younger age patients with Ewing sarcoma. In Epigenetics, 8, 893-8. doi:10.4161/epi.25617. https://pubmed.ncbi.nlm.nih.gov/23887284/

7. Guerrero-Setas, David, Pérez-Janices, Noemí, Blanco-Fernandez, Laura, Torrea, Natalia, Guarch, Rosa. 2013. RASSF2 hypermethylation is present and related to shorter survival in squamous cervical cancer. In Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 26, 1111-22. doi:10.1038/modpathol.2013.32. https://pubmed.ncbi.nlm.nih.gov/23542458/

8. Barnoud, Thibaut, Wilkey, Daniel W, Merchant, Michael L, Clark, Jennifer A, Donninger, Howard. 2016. Proteomics Analysis Reveals Novel RASSF2 Interaction Partners. In Cancers, 8, . doi:10.3390/cancers8030037. https://pubmed.ncbi.nlm.nih.gov/26999212/

9. Vos, Michele D, Ellis, Chad A, Elam, Candice, Taylor, Barbara J, Clark, Geoffrey J. 2003. RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor. In The Journal of biological chemistry, 278, 28045-51. doi:. https://pubmed.ncbi.nlm.nih.gov/12732644/