Trim67是一种三重基序(TRIM)家族蛋白,TRIM家族蛋白在多种重要的细胞过程中发挥作用,包括细胞凋亡、细胞周期阻滞、DNA修复和衰老。Trim67在结直肠癌和肺癌等多种癌症中发挥重要作用。在结直肠癌中,Trim67的表达下调与不良预后相关,而其高表达则能够抑制肿瘤的生长和转移[1,3]。此外,Trim67在神经系统的发育和功能中也有重要作用,如调控嗅球中僧帽细胞的增殖和突触发育[5]。
Trim67与p53信号通路有密切联系。在结直肠癌中,Trim67能够直接与p53的C端相互作用,抑制p53的降解,从而激活p53信号通路,发挥抑癌作用[1]。在肺癌中,Trim67的表达下调能够促进细胞凋亡和自噬,而ENAH蛋白能够与Trim67相互作用,抑制Trim67的表达,从而促进肺癌细胞凋亡和自噬[2]。此外,Trim67还能够与Ras信号通路相关蛋白相互作用,如80K-H,通过降解80K-H来抑制Ras信号通路,促进神经分化[6]。
Trim67的表达受到多种因素的调控。在结直肠癌中,Trim67的表达受到DNA甲基化的调控,其启动子区域的CpG岛存在显著的甲基化,导致Trim67表达下调[3]。在妊娠糖尿病中,胎盘组织中Trim67启动子区域的CpG岛也存在显著的甲基化,与血糖和血脂水平相关[4]。此外,Trim67的表达还受到miRNA的调控,如miR-766-5p,能够与Trim67相互作用,抑制Trim67的表达[7]。
综上所述,Trim67是一种重要的TRIM家族蛋白,在多种癌症和神经系统发育中发挥重要作用。Trim67通过多种信号通路发挥功能,如p53信号通路、Ras信号通路和NF-κB信号通路等。Trim67的表达受到多种因素的调控,包括DNA甲基化和miRNA等。Trim67的研究有助于深入理解TRIM家族蛋白的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Wang, Shiyan, Zhang, Yanquan, Huang, Junzhe, Zhao, Zengren, Yu, Jun. 2019. TRIM67 Activates p53 to Suppress Colorectal Cancer Initiation and Progression. In Cancer research, 79, 4086-4098. doi:10.1158/0008-5472.CAN-18-3614. https://pubmed.ncbi.nlm.nih.gov/31239268/
2. Liu, Rui, Miao, Kun, Gao, Ling, He, Ling. . TRIM67 interacts with ENAH to regulate the apoptosis and autophagy of lung cancer cells. In General physiology and biophysics, 43, 163-173. doi:10.4149/gpb_2023037. https://pubmed.ncbi.nlm.nih.gov/38477606/
3. Liu, Ying, Wang, Guiqi, Jiang, Xia, Zhao, Zengren, Yu, Weifang. 2020. TRIM67 inhibits tumor proliferation and metastasis by mediating MAPK11 in Colorectal Cancer. In Journal of Cancer, 11, 6025-6037. doi:10.7150/jca.47538. https://pubmed.ncbi.nlm.nih.gov/32922543/
4. Chen, Fujia, Fei, Xiaoping, Zhu, Weiqiang, Li, Min, Du, Jing. 2022. Placental DNA methylation changes in gestational diabetes mellitus. In Epigenetics, 17, 2109-2121. doi:10.1080/15592294.2022.2110193. https://pubmed.ncbi.nlm.nih.gov/35993280/
5. Cai, Chunyu, Luo, Qihui, Jia, Lanlan, Huang, Chao, Chen, Zhengli. 2023. TRIM67 Implicates in Regulating the Homeostasis and Synaptic Development of Mitral Cells in the Olfactory Bulb. In International journal of molecular sciences, 24, . doi:10.3390/ijms241713439. https://pubmed.ncbi.nlm.nih.gov/37686246/
6. Yaguchi, Hiroaki, Okumura, Fumihiko, Takahashi, Hidehisa, Sasaki, Hidenao, Hatakeyama, Shigetsugu. 2012. TRIM67 protein negatively regulates Ras activity through degradation of 80K-H and induces neuritogenesis. In The Journal of biological chemistry, 287, 12050-9. doi:10.1074/jbc.M111.307678. https://pubmed.ncbi.nlm.nih.gov/22337885/
7. Li, Chen, Li, Xu. 2022. Exosome-Derived Circ_0094343 Promotes Chemosensitivity of Colorectal Cancer Cells by Regulating Glycolysis via the miR-766-5p/TRIM67 Axis. In Contrast media & molecular imaging, 2022, 2878557. doi:10.1155/2022/2878557. https://pubmed.ncbi.nlm.nih.gov/35854778/