Rab7基因,也称为RAB7A,是Rab GTP酶家族成员之一,广泛存在于真核细胞中,参与调控内吞作用、自噬作用和细胞内囊泡运输等生物学过程。Rab7在细胞内囊泡运输中发挥着关键作用,它能够识别特定的囊泡,并招募相应的运输蛋白,从而实现囊泡的定向运输和融合。此外,Rab7还参与自噬作用,通过调节自噬泡的形成和与溶酶体的融合,促进细胞内受损或衰老细胞器的清除和降解。
研究表明,Rab7基因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瘤等。在动脉粥样硬化中,Rab7基因的表达上调,导致细胞内囊泡运输异常,从而促进动脉粥样硬化斑块的形成[4]。在糖尿病心肌病中,Rab7基因的表达下调,导致细胞内自噬作用受损,从而促进糖尿病心肌病的发生[1]。在结直肠癌中,Rab7基因的表达下调,导致细胞内囊泡运输异常,从而促进肿瘤的转移[2]。此外,Rab7基因的表达下调还与儿童Wilms瘤的易感性降低相关[3]。
高风险神经母细胞瘤(NB)患者中,Rab7基因的表达显著上调,与不良预后有强相关性。Rab7基因通过调节PI3K/AKT信号通路,促进NB细胞的活性,从而促进肿瘤的发生和发展[5]。此外,Rab7基因还可以通过影响组蛋白修饰,进而调控二价结构基因的表达[6]。
Rab7基因不仅在RNA修饰中发挥作用,还具有独立的染色质调控功能。Rab7基因可以与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,Rab7基因还可以通过下调lncRNA XIST的表达抑制结直肠癌的增殖和转移[8]。
综上所述,Rab7基因是一种重要的Rab GTP酶,参与调控内吞作用、自噬作用和细胞内囊泡运输等生物学过程。Rab7基因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瘤等。此外,Rab7基因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。Rab7基因的研究有助于深入理解内吞作用、自噬作用和细胞内囊泡运输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. Piper, Bryce, Bogamuwa, Srimathi, Hossain, Tanvir, Eckmann, David M, Farkas, Laszlo. 2024. RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension. In The Journal of clinical investigation, 134, . doi:10.1172/JCI169441. https://pubmed.ncbi.nlm.nih.gov/38015641/
2. Shen, Chenjie, Liu, Jinging, Liu, Huan, Mao, Yong, Hua, Dong. 2023. Timosaponin AIII induces lipid peroxidation and ferroptosis by enhancing Rab7-mediated lipophagy in colorectal cancer cells. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 122, 155079. doi:10.1016/j.phymed.2023.155079. https://pubmed.ncbi.nlm.nih.gov/37863004/
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8. Rodriguez-Furlan, Cecilia, Borna, Rita, Betz, Oliver. 2023. RAB7 GTPases as coordinators of plant endomembrane traffic. In Frontiers in plant science, 14, 1240973. doi:10.3389/fpls.2023.1240973. https://pubmed.ncbi.nlm.nih.gov/37662169/