SAMD5, or Sterile Alpha Motif Domain Containing 5, is a gene that has been implicated in multiple biological processes and disease conditions. It has been associated with cell cycle regulation and may play a role in various signaling pathways [4]. Given its connections to cell-related functions, genetic models such as gene knockout (KO) or conditional knockout (CKO) mouse models could potentially be valuable in further elucidating its functions.

In prostate cancer, SAMD5 mRNA is overexpressed and can predict biochemical recurrence after radical prostatectomy, independent of Gleason score and pathologic T-stage, indicating its role in this cancer's prognosis [2]. In biliary tree-related diseases, SAMD5 is expressed in biliary tree stem/progenitor cells at the peribiliary gland but not in liver stem/progenitor cells in mice. In humans, its expression and location could be a diagnostic marker for bile duct and cholangiocarcinoma cell type and malignancy, and in vitro experiments suggest it is associated with the cell cycle regulation of cholangiocarcinoma cell lines [4]. In breast cancer, particularly triple-negative breast cancer, SAMD5 acts as a tumor suppressor by inhibiting cellular processes and downregulating the c-Myc signaling pathway, with this effect mediated in part through its negative association with Polo-like Kinase 1 (PLK1) [5]. Gene fusions involving SAMD5, such as SAMD5-SASH1, have been identified in solitary infantile myofibromatosis, skull base chordoma, and MYCN non-amplified neuroblastoma, mainly in non-high-risk patients with ganglioneuroblastoma histology [1,6,7]. Also, in COPD, the RNA-binding protein AZGP1 may regulate SAMD5 expression to modulate AT2 cell proliferation and adhesion [3].

In conclusion, SAMD5 is involved in cell-related processes and plays important roles in multiple diseases including prostate cancer, cholangiocarcinoma, breast cancer, and potentially in COPD. The findings from various studies, some potentially related to in vivo models, contribute to understanding its functions in disease development and progression, providing insights for potential diagnostic and therapeutic strategies.

References:

1. Yamashita, Motoi, Kuroha, Masae, Kinowawki, Yuko, Morio, Tomohiro, Takagi, Masatoshi. 2023. A SAMD5-SASH1 fusion in solitary infantile myofibromatosis. In Pediatric blood & cancer, 70, e30278. doi:10.1002/pbc.30278. https://pubmed.ncbi.nlm.nih.gov/36861442/

2. Li, Fei, Xu, Yong, Liu, Ran-Lu. 2019. SAMD5 mRNA was overexpressed in prostate cancer and can predict biochemical recurrence after radical prostatectomy. In International urology and nephrology, 51, 443-451. doi:10.1007/s11255-019-02096-3. https://pubmed.ncbi.nlm.nih.gov/30739268/

3. Shen, Wen, Wei, Wei, Wang, Shukun, Wang, Ruili, Tian, Hong. 2024. RNA-binding protein AZGP1 inhibits epithelial cell proliferation by regulating the genes of alternative splicing in COPD. In Gene, 927, 148736. doi:10.1016/j.gene.2024.148736. https://pubmed.ncbi.nlm.nih.gov/38950687/

4. Yagai, Tomoki, Matsui, Satoshi, Harada, Kenichi, Miyajima, Atsushi, Tanaka, Minoru. 2017. Expression and localization of sterile alpha motif domain containing 5 is associated with cell type and malignancy of biliary tree. In PloS one, 12, e0175355. doi:10.1371/journal.pone.0175355. https://pubmed.ncbi.nlm.nih.gov/28388653/

5. Tuo, YouLin, Ye, YiFeng. 2024. Sterile Alpha Motif Domain-Containing 5 Suppresses Malignant Phenotypes and Tumor Growth in Breast Cancer: Regulation of Polo-Like Kinase 1 and c-Myc Signaling in a Xenograft Model. In Cureus, 16, e73259. doi:10.7759/cureus.73259. https://pubmed.ncbi.nlm.nih.gov/39524172/

6. Sa, Jason K, Lee, In-Hee, Hong, Sang Duk, Kong, Doo-Sik, Nam, Do-Hyun. . Genomic and transcriptomic characterization of skull base chordoma. In Oncotarget, 8, 1321-1328. doi:10.18632/oncotarget.13616. https://pubmed.ncbi.nlm.nih.gov/27901492/

7. Lee, Eunjin, Lee, Ji Won, Lee, Boram, Sung, Ki Woong, Park, Woong-Yang. 2020. Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma. In BMC medical genomics, 13, 171. doi:10.1186/s12920-020-00819-5. https://pubmed.ncbi.nlm.nih.gov/33172452/