Sfmbt1-KO Mouse

Sfmbt1, short for Scm-like with four malignant brain tumor domains 1, is a mammalian MBT domain-containing protein homologous to Drosophila SFMBT. It acts as a transcriptional repressor and is involved in epigenetic regulation of gene expression. SFMBT1 forms a stable complex with LSD1 and CoREST to regulate transcription in somatic cells and spermatogenesis, causing chromatin compaction and transcriptional repression of target genes like replication-dependent histones [3].

In colorectal cancer (CRC), SFMBT1 is up-regulated, especially in 5-fluorouracil (5-FU) resistance cases. It drives 5-FU resistance, CRC cell proliferation, migration, and invasion, and is positively correlated with HMG20A. Depletion of SFMBT1 down-regulates HMG20A downstream, as verified by murine xenograft and lung metastasis models, suggesting the SFMBT1/HMG20A axis could be a target to increase CRC cells' sensitivity to 5-FU [1]. In clear cell renal cell carcinomas (ccRCC) with VHL loss-of-function mutations, SFMBT1 protein levels are elevated. Depletion of SFMBT1 abolishes ccRCC cell proliferation in vitro and inhibits orthotopic tumor growth in vivo, with sphingosine kinase 1 (SPHK1) identified as a key target gene [2]. In cervical cancer, miR-218 can inhibit the invasion and migration of cells by inhibiting the expression of SFMBT1 [4]. Also, in ccRCC, the combined high expression of SFMBT1 and ZHX2 is significantly associated with overall survival and disease-free survival, and is an independent prognostic factor [5].

In summary, SFMBT1 is crucial in epigenetic regulation and transcriptional repression. Through gene-knockout or knockdown models in various cancer studies, its role in promoting cancer cell proliferation, migration, invasion, and drug resistance has been revealed, highlighting its potential as a therapeutic target in CRC and ccRCC. Additionally, its association with other genes like HMG20A and ZHX2 provides further insights into cancer-related mechanisms [1,2,4,5].

References:

1. Pan, Ruijun, Yu, Dingye, Hu, Jiajia, Zhang, Xiaoping, Cai, Wei. 2022. SFMBT1 facilitates colon cancer cell metastasis and drug resistance combined with HMG20A. In Cell death discovery, 8, 263. doi:10.1038/s41420-022-01057-7. https://pubmed.ncbi.nlm.nih.gov/35577773/

2. Liu, Xijuan, Simon, Jeremy M, Xie, Haibiao, Gong, Kan, Zhang, Qing. 2020. Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss. In Molecular cell, 77, 1294-1306.e5. doi:10.1016/j.molcel.2020.01.009. https://pubmed.ncbi.nlm.nih.gov/32023483/

3. Zhang, Jin, Bonasio, Roberto, Strino, Francesco, Cohen, Paula E, Reinberg, Danny. . SFMBT1 functions with LSD1 to regulate expression of canonical histone genes and chromatin-related factors. In Genes & development, 27, 749-66. doi:10.1101/gad.210963.112. https://pubmed.ncbi.nlm.nih.gov/23592795/

4. Li, Huan, An, Xuzhuo, Fu, Qiaoshan. 2022. MiR-218 Affects the Invasion and Metastasis of Cervical Cancer Cells by Inhibiting the Expression of SFMBT1 and DCUNIDI. In Cellular and molecular biology (Noisy-le-Grand, France), 68, 81-86. doi:10.14715/cmb/2022.68.2.12. https://pubmed.ncbi.nlm.nih.gov/35869720/

5. Chen, Yufeng, Zhu, Liangsong, Xue, Song, He, Chunfeng, Zhang, Qingchuan. 2021. Novel VHL substrate targets SFMBT1 and ZHX2 may be important prognostic predictors in patients with ccRCC. In Oncology letters, 21, 379. doi:10.3892/ol.2021.12640. https://pubmed.ncbi.nlm.nih.gov/33777203/