Snd1, also known as Tudor-SN, TSN or p100, encodes an evolutionarily conserved protein. It contains four repeated staphylococcal nuclease domains and a single Tudor domain, endowing it with endonuclease activity and a high capacity for interacting with nucleic acids, proteins and protein complexes. Snd1 plays fundamental roles in gene expression regulation, including RNA splicing, interference, stability and editing, as well as in the regulation of protein and lipid homeostasis. It is also involved in multiple cellular processes and has been linked to various diseases, making genetic models valuable for its study [1,3].

In prostate cancer models (PB-Cre/Ptenflox/flox/ERG mice), prostate-specific Snd1 deletion reduces cancer growth and tumor burden. Knocking down Snd1 in human prostate epithelial cells, especially those overexpressing ERG, negatively impacts cell proliferation, highlighting Snd1's crucial role in prostate tumorigenesis [2]. In liver cancer, Snd1 localized to mitochondria promotes phosphoglycerate mutase 5 (PGAM5)-mediated mitophagy, and its aberrant expression predicts poor outcomes in hepatocellular carcinoma patients [4]. Also, in esophageal squamous cell carcinoma cells, knockdown of Snd1 increases genotoxin sensitivity, suggesting its role in cancer chemoresistance [5].

In conclusion, Snd1 is involved in essential biological functions such as gene expression regulation and lipid metabolism. Model-based research, especially through Snd1 KO/CKO mouse models, has revealed its significance in diseases like prostate cancer, liver cancer and esophageal squamous cell carcinoma, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Ochoa, Begoña, Chico, Yolanda, Martínez, María José. 2018. Insights Into SND1 Oncogene Promoter Regulation. In Frontiers in oncology, 8, 606. doi:10.3389/fonc.2018.00606. https://pubmed.ncbi.nlm.nih.gov/30619748/

2. Liao, Sheng-You, Rudoy, Dmytro, Frank, Sander B, Emili, Andrew, Vasioukhin, Valeri. 2023. SND1 binds to ERG and promotes tumor growth in genetic mouse models of prostate cancer. In Nature communications, 14, 7435. doi:10.1038/s41467-023-43245-8. https://pubmed.ncbi.nlm.nih.gov/37973913/

3. Navarro-Imaz, Hiart, Ochoa, Begoña, García-Arcos, Itsaso, Fresnedo, Olatz, Rueda, Yuri. 2020. Molecular and cellular insights into the role of SND1 in lipid metabolism. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1865, 158589. doi:10.1016/j.bbalip.2019.158589. https://pubmed.ncbi.nlm.nih.gov/31978555/

4. Liang, Shiwei, Zhu, Chuxu, Suo, Caixia, Sun, Linchong, Gao, Ping. 2022. Mitochondrion-Localized SND1 Promotes Mitophagy and Liver Cancer Progression Through PGAM5. In Frontiers in oncology, 12, 857968. doi:10.3389/fonc.2022.857968. https://pubmed.ncbi.nlm.nih.gov/35433434/

5. Wu, Jian, Jiang, Yixin, Zhang, Qin, Qiu, Lei, Han, Junhong. . KDM6A-SND1 interaction maintains genomic stability by protecting the nascent DNA and contributes to cancer chemoresistance. In Nucleic acids research, 52, 7665-7686. doi:10.1093/nar/gkae487. https://pubmed.ncbi.nlm.nih.gov/38850159/