ABTB2基因,也称为BPOZ-2或Bood POZ containing gene type 2,编码一种含有Broad-Complex, Tramtrack, and Bric a brac (BTB/POZ)结构域的蛋白,其作为一种支架蛋白,与E3泛素连接酶Cullin 3相互作用,参与调节多种生物蛋白的降解。这种蛋白参与胚胎发育到肿瘤进展等多个生物学过程,并在多种疾病中发挥重要作用。
ABTB2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。在动脉粥样硬化中,ABTB2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,ABTB2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,ABTB2通过m6A修饰抑制SOX4 mRNA的表达,从而抑制肿瘤的转移[3]。此外,ABTB2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,ABTB2表达显著上调,与不良预后有强相关性。ABTB2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]。ABTB2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]。
ABTB2不仅在RNA修饰中发挥作用,还具有独立的染色质调控功能。ABTB2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,ABTB2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,ABTB2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。ABTB2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,ABTB2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。ABTB2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。
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