GSE1, also known as KIAA0182, is a proline-rich protein. It is a component of the CoREST complex, which acts as an H3K4 and H3K9 demethylase and regulates gene expression. GSE1 is involved in the DNA damage response (DDR) pathway, as it forms a complex with the HDAC1/CoREST deacetylase/demethylase co-repressor complex and plays a role in histone modification and DNA damage sensing during DDR [1].

Gse1 has been studied using gene knockout models. Maternal or zygotic deletion of Gse1 in mice leads to prenatal death, embryonic lethality from E12.5, and perinatal death, indicating its essential role in mouse development, especially in placenta development [2]. In cancer research, loss-of-function experiments in various cancer cell lines have shown that depletion of GSE1 inhibits the proliferation, migration, and invasion of lung adenocarcinoma, breast cancer, gastric cancer, and castration-resistant prostate cancer cells [3,4,5,7]. In AML, pharmacological inhibition of LSD1 downregulates GSE1, leading to myeloid differentiation [6].

In conclusion, GSE1 is crucial for normal development, especially placenta development in mice. In disease, particularly in cancer, GSE1 often acts as an oncogene promoting cancer cell growth, migration, and resistance to therapies. Gene knockout and related functional studies of GSE1 in mouse models and cell lines have provided valuable insights into its role in normal biological processes and disease conditions, potentially guiding the development of new cancer therapies.

References:

1. Vcelkova, Terezia, Reiter, Wolfgang, Zylka, Martha, Hartl, Markus, Seiser, Christian. . GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage. In Nucleic acids research, 51, 11748-11769. doi:10.1093/nar/gkad911. https://pubmed.ncbi.nlm.nih.gov/37878419/

2. Hiver, Sylvain, Shimizu-Mizuno, Natsumi, Ikawa, Yayoi, Tanaka, Satoshi, Hamada, Hiroshi. 2023. Gse1, a component of the CoREST complex, is required for placenta development in the mouse. In Developmental biology, 498, 97-105. doi:10.1016/j.ydbio.2023.03.009. https://pubmed.ncbi.nlm.nih.gov/37019373/

3. Meng, Ziyu, Yang, Yingqian, Li, Shupei, Wang, Wenbin, Wang, Fengsong. 2024. GSE1 promotes the proliferation and migration of lung adenocarcinoma cells by downregulating KLF6 expression. In Cell biology international, 48, 1490-1506. doi:10.1002/cbin.12208. https://pubmed.ncbi.nlm.nih.gov/38886911/

4. Chai, Peng, Tian, Jingzhong, Zhao, Deyin, Ding, Keshuo, Liu, Bin. 2016. GSE1 negative regulation by miR-489-5p promotes breast cancer cell proliferation and invasion. In Biochemical and biophysical research communications, 471, 123-8. doi:10.1016/j.bbrc.2016.01.168. https://pubmed.ncbi.nlm.nih.gov/26828271/

5. Ding, Keshuo, Tan, Sheng, Huang, Xing, Wang, Wenbin, Wu, Zhengsheng. 2018. GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis. In The Journal of biological chemistry, 293, 3949-3964. doi:10.1074/jbc.RA117.001103. https://pubmed.ncbi.nlm.nih.gov/29367342/

6. Nicosia, Luciano, Boffo, Francesca Ludovica, Ceccacci, Elena, Minucci, Saverio, Bonaldi, Tiziana. 2021. Pharmacological inhibition of LSD1 triggers myeloid differentiation by targeting GSE1 oncogenic functions in AML. In Oncogene, 41, 878-894. doi:10.1038/s41388-021-02123-7. https://pubmed.ncbi.nlm.nih.gov/34862459/

7. Bamodu, Oluwaseun Adebayo, Wang, Yuan-Hung, Ho, Chen-Hsun, Chen, Kuan-Chou, Wu, Chia-Chang. 2021. Genetic Suppressor Element 1 (GSE1) Promotes the Oncogenic and Recurrent Phenotypes of Castration-Resistant Prostate Cancer by Targeting Tumor-Associated Calcium Signal Transducer 2 (TACSTD2). In Cancers, 13, . doi:10.3390/cancers13163959. https://pubmed.ncbi.nlm.nih.gov/34439112/