GRAMD1C,也称为Aster-C,是一种内质网(ER)驻留蛋白,主要负责将胆固醇从质膜转运到ER。尽管其同源蛋白Aster-B在胆固醇转运和下游酯化中发挥重要作用,但Aster-C在胆固醇稳态中的具体角色尚不明确。已有研究表明,在低或高膳食胆固醇条件下,缺乏Aster-C的小鼠体内,粪便、肝脏或血浆中的胆固醇水平没有显著变化。然而,当膳食胆固醇有限时,缺乏Aster-C的小鼠的某些胆酸种类水平略有降低,皮质醇水平升高。此外,肝脏RNA测序显示,缺乏Aster-C的小鼠在低膳食胆固醇条件下,主要尿蛋白和细胞色素P450(CYP)家族的基因表达发生改变。这些数据表明,Aster-C对全身胆固醇转运和代谢的影响较小,但在膳食胆固醇有限时,可能会对循环皮质醇和胆酸水平产生轻微影响[3]。
GRAMD1C在多种生物学过程中发挥作用,包括炎症反应、细胞周期和肝脏代谢功能。已有研究表明,GRAMD1C在多种疾病中具有潜在的诊断和预后价值。例如,在乳腺癌中,GRAMD1C表达下调与肿瘤的侵袭性和不良预后相关[1]。此外,GRAMD1C还与儿童败血症的诊断相关[2]。在胆管癌中,GRAMD1C表达下调与肿瘤细胞增殖和迁移能力降低相关[6]。此外,GRAMD1C还与亨廷顿病(HD)的发生发展相关,其表达水平在HD的不同阶段发生改变[7]。在肝细胞癌(HCC)中,GRAMD1C表达上调与肿瘤的发生发展和不良预后相关[4][5]。此外,GRAMD1C还与非肝硬化性肝细胞癌(NCHCC)的预后相关,其表达水平可以预测患者的生存时间[5]。
GRAMD1C在多种疾病中发挥重要作用,其表达水平与疾病的诊断和预后相关。此外,GRAMD1C还可能影响胆固醇稳态、细胞凋亡、炎症反应、细胞周期和肝脏代谢功能。GRAMD1C的研究有助于深入理解其在多种生物学过程中的作用机制,为疾病的治疗和预防提供新的思路和策略。
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