Dpf3-KO Mouse

DPF3, a component of the SWI/SNF chromatin remodeling complex, is involved in various biological processes such as cell growth, proliferation, apoptosis, and motility [3,7]. It has been associated with pathways like TGF-β signaling and is crucial for maintaining normal cellular functions and may play a role in chromatin remodeling and gene expression regulation [2,4].

In dendritic cells, a long non-coding RNA lnc-Dpf3, induced by CCR7 chemokine receptor stimulation, restrains dendritic cell migration by inhibiting HIF-1α-mediated glycolysis. DC-specific lnc-Dpf3 deficiency increases CCR7-mediated DC migration, leading to exaggerated adaptive immune responses and inflammatory injuries [1]. In clear cell renal cell carcinoma (ccRCC), the short isoform DPF3a promotes kidney cancer cell migration both in vitro and in vivo, by interacting with SNIP1, forming a complex with SMAD4 and p300 HAT, and activating cell movement related genes [2]. In breast cancer, downregulation of DPF3 promotes cell proliferation and motility through activating JAK2/STAT3 signaling [6]. Also, in renal cancer, germline variation in DPF3 can lead to reduced apoptosis and activation of the STAT3 pathway, and the risk allele at 14q24.2 activates a hypoxia-inducible transcription factor-binding enhancer of DPF3 expression, increasing the risk of developing renal cancer [7,8]. Polymorphisms in DPF3 are associated with an increased risk of pulmonary tuberculosis in the Northwest Chinese Han population [5].

In summary, DPF3 is involved in multiple biological processes and its dysregulation is associated with various diseases including cancer and pulmonary tuberculosis. Studies, such as those using cell-specific knockouts in dendritic cells, have revealed its role in immune responses and disease-related cell behaviors, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Liu, Juan, Zhang, Xiaomin, Chen, Kun, Li, Zhiqing, Cao, Xuetao. 2019. CCR7 Chemokine Receptor-Inducible lnc-Dpf3 Restrains Dendritic Cell Migration by Inhibiting HIF-1α-Mediated Glycolysis. In Immunity, 50, 600-615.e15. doi:10.1016/j.immuni.2019.01.021. https://pubmed.ncbi.nlm.nih.gov/30824325/

2. Cui, Huanhuan, Yi, Hongyang, Bao, Hongyu, Hu, Yuhui, Chen, Wei. 2022. The SWI/SNF chromatin remodeling factor DPF3 regulates metastasis of ccRCC by modulating TGF-β signaling. In Nature communications, 13, 4680. doi:10.1038/s41467-022-32472-0. https://pubmed.ncbi.nlm.nih.gov/35945219/

3. Druml, Thomas, Brem, Gottfried, Horna, Michaela, Ricard, Anne, Grilz-Seger, Gertrud. 2021. DPF3, A Putative Candidate Gene For Melanoma Etiopathogenesis in Gray Horses. In Journal of equine veterinary science, 108, 103797. doi:10.1016/j.jevs.2021.103797. https://pubmed.ncbi.nlm.nih.gov/34801788/

4. Verrillo, Giulia, Obeid, Anna Maria, Genco, Alexia, Martin, Maud, Mottet, Denis. 2024. Non-canonical role for the BAF complex subunit DPF3 in mitosis and ciliogenesis. In Journal of cell science, 137, . doi:10.1242/jcs.261744. https://pubmed.ncbi.nlm.nih.gov/38661008/

5. Liu, Changchun, Chen, Mingyue, Xu, Jinpeng, He, Shumei, Jin, Tianbo. 2024. DPF3 polymorphisms increased the risk of pulmonary tuberculosis in the Northwest Chinese Han population. In Gene, 927, 148617. doi:10.1016/j.gene.2024.148617. https://pubmed.ncbi.nlm.nih.gov/38795855/

6. Lin, Wei-Hao, Dai, Wei-Gang, Xu, Xiang-Dong, Li, Jie, Li, He-Ping. 2019. Downregulation of DPF3 promotes the proliferation and motility of breast cancer cells through activating JAK2/STAT3 signaling. In Biochemical and biophysical research communications, 514, 639-644. doi:10.1016/j.bbrc.2019.04.170. https://pubmed.ncbi.nlm.nih.gov/31076105/

7. Colli, Leandro M, Jessop, Lea, Myers, Timothy A, Brown, Kevin M, Chanock, Stephen J. 2021. Altered regulation of DPF3, a member of the SWI/SNF complexes, underlies the 14q24 renal cancer susceptibility locus. In American journal of human genetics, 108, 1590-1610. doi:10.1016/j.ajhg.2021.07.009. https://pubmed.ncbi.nlm.nih.gov/34390653/

8. Protze, Johanna, Naas, Stephanie, Krüger, René, Wullich, Bernd, Schödel, Johannes. 2022. The renal cancer risk allele at 14q24.2 activates a novel hypoxia-inducible transcription factor-binding enhancer of DPF3 expression. In The Journal of biological chemistry, 298, 101699. doi:10.1016/j.jbc.2022.101699. https://pubmed.ncbi.nlm.nih.gov/35148991/