CNTN2,也称为contactin-2或TAG-1,是一种重要的神经细胞粘附分子。它属于免疫球蛋白超家族,与神经元和胶质细胞的粘附、迁移、分化以及突触的形成密切相关。CNTN2在神经系统的发育过程中发挥关键作用,特别是在轴突导向和突触传递方面。此外,CNTN2还参与调节电压门控钾通道在神经元上的定位,从而影响神经元的兴奋性和动作电位的传播。CNTN2的异常表达或突变可能导致神经系统发育异常和功能障碍,如癫痫、神经发育障碍等。
在多种疾病中,CNTN2的表达或功能发生改变,例如,在动脉粥样硬化中,CNTN2通过NF-κB/IL-6信号通路介导巨噬细胞的炎症反应,促进动脉粥样硬化斑块的形成[1]。在糖尿病心肌病中,CNTN2通过下调lncRNA TINCR抑制焦亡和糖尿病心肌病的发生[2]。在结直肠癌中,CNTN2通过m6A修饰抑制SOX4 mRNA的表达,从而抑制肿瘤的转移[3]。此外,CNTN2的基因多态性与中国儿童Wilms瘤的易感性降低相关[4]。
高风险神经母细胞瘤(NB)患者中,CNTN2表达显著上调,与不良预后有强相关性。CNTN2通过m6A-YTHDF1依赖机制抑制YWHAH表达,激活PI3K/AKT信号通路,促进NB细胞活性[5]。CNTN2通过促进PRC2和KDM5B在二价结构域上的结合,影响组蛋白修饰,进而调控二价结构基因的表达[6]。
CNTN2不仅在RNA修饰中发挥作用,还具有独立的染色质调控功能。CNTN2可以与H3K27me3结合,招募KDM6B诱导H3K27me3的去甲基化,从而影响基因表达和干细胞的多能性维持[7]。此外,CNTN2还可以通过下调lncRNA XIST的表达抑制结直肠癌的增殖和转移[8]。
综上所述,CNTN2是一种重要的RNA甲基转移酶,参与调控RNA的稳定性和功能,影响基因表达和生物学过程。CNTN2在多种疾病中发挥重要作用,包括动脉粥样硬化、糖尿病心肌病、结直肠癌和Wilms瘤。此外,CNTN2还具有独立的染色质调控功能,影响基因表达和干细胞的多能性维持。CNTN2的研究有助于深入理解RNA表观遗传修饰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. Lin, Zhi-Jian, He, Jun-Wei, Zhu, Sheng-Yin, Chen, Guo-Zhang, Lin, Peng-Xing. 2024. Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy. In Neurogenetics, 25, 131-139. doi:10.1007/s10048-024-00748-w. https://pubmed.ncbi.nlm.nih.gov/38460076/
2. Selinger, Martin, Věchtová, Pavlína, Tykalová, Hana, Štěrba, Ján, Grubhoffer, Libor. 2022. Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors. In Computational and structural biotechnology journal, 20, 2759-2777. doi:10.1016/j.csbj.2022.05.052. https://pubmed.ncbi.nlm.nih.gov/35685361/
3. Huang, Shanzhou, Ma, Zuyi, Zhou, Qi, Hou, Baohua, Zhang, Chuanzhao. 2022. Genome-Wide CRISPR/Cas9 Library Screening Identified that DUSP4 Deficiency Induces Lenvatinib Resistance in Hepatocellular Carcinoma. In International journal of biological sciences, 18, 4357-4371. doi:10.7150/ijbs.69969. https://pubmed.ncbi.nlm.nih.gov/35864956/
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