Fam120a, also known as OSSA/C9ORF10, is a multi-functional gene. It functions as a transcription co-activator, an RNA-binding protein, and a scaffold protein. It is involved in pathways such as mTORC1-serine/arginine-rich protein kinase 2 (SRPK2) signaling, which couples transcription and splicing of de novo lipid synthesis enzymes [1]. It also participates in processes like ferroptosis regulation, RNA interference modulation, and is associated with cell growth and cancer-related pathways.

In gastric cancer, FAM120A deficiency promotes ferroptosis, enhancing cisplatin sensitivity, indicating its role in chemotherapy tolerance [2]. In colon cancer, FAM120A acts as a key mediator in the IL13/IL13Rα2 signaling pathway for invasion and liver metastasis, as its silencing abolishes IL13-induced cell migration, invasion, and survival [4]. In addition, a circular RNA, circFAM120A, promotes cell proliferation by preventing FAM120A mRNA from binding the translation inhibitor IGF2BP2 [3].

In conclusion, Fam120a is crucial in various biological processes and disease conditions. Its role in cancer, such as in gastric and colon cancer, as revealed through functional studies including gene silencing (akin to loss-of-function in KO models), highlights its potential as a therapeutic target. The gene also impacts lipid metabolism-related transcription and splicing, contributing to our understanding of anabolic cell growth regulation.

References:

1. Cho, Sungyun, Chun, Yujin, He, Long, Blenis, John, Lee, Gina. . FAM120A couples SREBP-dependent transcription and splicing of lipogenesis enzymes downstream of mTORC1. In Molecular cell, 83, 3010-3026.e8. doi:10.1016/j.molcel.2023.07.017. https://pubmed.ncbi.nlm.nih.gov/37595559/

2. Niu, Liangbo, Li, Yi, Huang, Guixiang, Fu, Jing, Feng, Lu. 2024. FAM120A deficiency improves resistance to cisplatin in gastric cancer by promoting ferroptosis. In Communications biology, 7, 399. doi:10.1038/s42003-024-06097-6. https://pubmed.ncbi.nlm.nih.gov/38565940/

3. Li, Siqi, Li, Xiang, Xue, Wei, Yang, Li, Chen, Ling-Ling. 2020. Screening for functional circular RNAs using the CRISPR-Cas13 system. In Nature methods, 18, 51-59. doi:10.1038/s41592-020-01011-4. https://pubmed.ncbi.nlm.nih.gov/33288960/

4. Bartolomé, Rubén A, García-Palmero, Irene, Torres, Sofía, Balyasnikova, Irina V, Casal, J Ignacio. 2015. IL13 Receptor α2 Signaling Requires a Scaffold Protein, FAM120A, to Activate the FAK and PI3K Pathways in Colon Cancer Metastasis. In Cancer research, 75, 2434-44. doi:10.1158/0008-5472.CAN-14-3650. https://pubmed.ncbi.nlm.nih.gov/25896327/