SOX12, a member of the SoxC group, is a crucial transcription factor. It is involved in various biological processes, and has been associated with multiple signaling pathways such as Wnt/β -catenin, JAK2/STAT3, and TGF -β1/TGFβR1-Smad2/3/4. It plays significant roles in cancer development, immune cell differentiation, and stem-cell-like phenotypes, making it an important target for understanding disease mechanisms [1-3].

In hepatocellular carcinoma (HCC), hepatocyte-specific SOX12 knockout attenuates DEN/CCl4-induced HCC progression and metastasis, while hepatocyte-specific SOX12 knock-in accelerates these effects. SOX12 promotes HCC metastasis by transcriptionally activating CCL22 expression to recruit Tregs and upregulating CD274 expression to suppress CD8+T-cell infiltration [1]. In osteosarcoma, SOX12 knockdown inhibits the spheroidization, expression of stemness markers, and tumor formation in nude mice [2]. In multiple myeloma, SOX12 knockdown reduces cell proliferation, colony formation, and upregulates apoptosis, and SOX12 inhibition retards tumor growth in a xenograft model [3].

In conclusion, SOX12 has diverse functions in different biological processes and diseases. Gene knockout and knock-in mouse models have been instrumental in revealing its role in promoting cancer progression, especially in HCC, osteosarcoma, and multiple myeloma. These models help in understanding the underlying molecular mechanisms, which may provide potential therapeutic targets for related diseases.

References:

1. Luo, Xiangyuan, Huang, Wenjie, Li, Siwen, Fan, Daiming, Xia, Limin. 2024. SOX12 Facilitates Hepatocellular Carcinoma Progression and Metastasis through Promoting Regulatory T-Cells Infiltration and Immunosuppression. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2310304. doi:10.1002/advs.202310304. https://pubmed.ncbi.nlm.nih.gov/39072947/

2. Zhang, Weifei, Yu, Fei, Weng, Jian, Wang, Deli, Zeng, Hui. 2021. SOX12 Promotes Stem Cell-Like Phenotypes and Osteosarcoma Tumor Growth by Upregulating JAGGED1. In Stem cells international, 2021, 9941733. doi:10.1155/2021/9941733. https://pubmed.ncbi.nlm.nih.gov/34725550/

3. Gao, Ying, Li, Lan, Hou, Limin, Ru, Xingli, Zhang, Ding. 2020. SOX12 promotes the growth of multiple myeloma cells by enhancing Wnt/β-catenin signaling. In Experimental cell research, 388, 111814. doi:10.1016/j.yexcr.2020.111814. https://pubmed.ncbi.nlm.nih.gov/31904384/