CELF2,也称为CUGBP Elav-like family member 2,是一种RNA结合蛋白,属于CELF RNA结合蛋白家族。该蛋白在多种生物学过程中发挥重要作用,包括RNA剪接、转运、编辑、稳定性和翻译。CELF2在多种细胞类型和组织中表达,并在细胞发育、分化和信号传导中发挥关键作用。CELF2在多种癌症中表达异常,包括急性髓系白血病(AML)、胶质母细胞瘤、结直肠癌和皮肤癌等。CELF2在AML中的作用机制研究表明,CELF2的缺失会导致FAT10 mRNA的稳定性增加,促进FAT10的翻译,从而增加AKT磷酸化和mTORC1信号通路的激活[1]。CELF2在胶质母细胞瘤中的作用机制研究表明,CELF2通过表观遗传抑制SOX3基因的表达,维持增殖/OLIG2细胞表型,具有克隆和致瘤性质[2]。CELF2在神经发育中的作用机制研究表明,CELF2的缺失会导致小鼠表现出社交障碍和焦虑等自闭症样行为,并干扰皮质神经元的晚期发育[3]。CELF2在结直肠癌中的作用机制研究表明,CELF2的表达在结直肠癌组织中降低,提示其可能是一种肿瘤抑制蛋白[4]。CELF2在皮肤癌中的作用机制研究表明,CELF2的缺失会促进皮肤肿瘤的发生和增加药物抗性[5]。CELF2在T细胞中的作用机制研究表明,CELF2在T细胞中表达增加,并具有位置依赖性的剪接调节活性[6]。CELF2在卵巢癌中的作用机制研究表明,CELF2通过稳定FAM198B来抑制卵巢癌的进展,并抑制MAPK/ERK信号通路[7]。
CELF2的研究表明,它在多种生物学过程中发挥重要作用,并在多种癌症中表达异常。CELF2的作用机制涉及RNA剪接、转运、编辑、稳定性和翻译等多个方面,并与多种信号通路相关。CELF2的研究有助于深入理解RNA结合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. Guo, Tengxiao, Wang, Yuxia, Sun, Xiaolu, Yuan, Weiping, Wang, Xiaomin. 2024. Loss of RNA-binding protein CELF2 promotes acute leukemia development via FAT10-mTORC1. In Oncogene, 43, 1476-1487. doi:10.1038/s41388-024-03006-3. https://pubmed.ncbi.nlm.nih.gov/38514854/
2. Turchi, Laurent, Sakakini, Nathalie, Saviane, Gaelle, Burel-Vandenbos, Fanny, Virolle, Thierry. 2023. CELF2 Sustains a Proliferating/OLIG2+ Glioblastoma Cell Phenotype via the Epigenetic Repression of SOX3. In Cancers, 15, . doi:10.3390/cancers15205038. https://pubmed.ncbi.nlm.nih.gov/37894405/
3. Duan, Xinyu, Peng, Xiaoxia, Jia, Xiangbin, Tan, Jieqiong, Hu, Zhangxue. 2024. CELF2 Deficiency Demonstrates Autism-Like Behaviors and Interferes with Late Development of Cortical Neurons in Mice. In Molecular neurobiology, 62, 156-168. doi:10.1007/s12035-024-04250-0. https://pubmed.ncbi.nlm.nih.gov/38829512/
4. Ramalingam, Satish, Ramamoorthy, Prabhu, Subramaniam, Dharmalingam, Anant, Shrikant. . Reduced Expression of RNA Binding Protein CELF2, a Putative Tumor Suppressor Gene in Colon Cancer. In Immuno-gastroenterology, 1, 27-33. doi:. https://pubmed.ncbi.nlm.nih.gov/23795348/
5. Sah, Bindeshwar, Singh, Jasvinder, Shen, Yao, Geskin, Larisa J, Liu, Liang. 2024. Loss of CELF2 promotes skin tumorigenesis and increases drug resistance. In International journal of dermatology, 64, 101-110. doi:10.1111/ijd.17295. https://pubmed.ncbi.nlm.nih.gov/38887832/
6. Ajith, Sandya, Gazzara, Matthew R, Cole, Brian S, Mallory, Michael J, Lynch, Kristen W. 2016. Position-dependent activity of CELF2 in the regulation of splicing and implications for signal-responsive regulation in T cells. In RNA biology, 13, 569-81. doi:10.1080/15476286.2016.1176663. https://pubmed.ncbi.nlm.nih.gov/27096301/
7. Guo, Qinhao, Wu, Yong, Guo, Xueqi, Ju, Xingzhu, Wu, Xiaohua. 2020. The RNA-Binding Protein CELF2 Inhibits Ovarian Cancer Progression by Stabilizing FAM198B. In Molecular therapy. Nucleic acids, 23, 169-184. doi:10.1016/j.omtn.2020.10.011. https://pubmed.ncbi.nlm.nih.gov/33335801/