SOX11/PRDX2轴调节了侵袭性地幔细胞淋巴瘤中的氧化还原稳定和化学抵抗
Anna De Bolòs1,2, Marta Sureda-Gómez1, Maria Carreras-Caballé1
1Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Scientific reports
|April 3, 2024
概括
带有SOX11过度表达的地幔细胞淋巴瘤 (MCL) 细胞表现出更高的活性氧物种 (ROS) 和PRDX2水平,有助于化学抵抗. 向PRDX2可能为侵袭性MCL提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 薄膜细胞淋巴瘤 (MCL) 是一种具有治疗反应不佳的侵袭性B细胞瘤.
- 过度表达SOX11与积极的MCL特征和更糟糕的患者结果有关.
- 氧化应激和SOX11在MCL氧化还原平衡中的作用在很大程度上是未知的.
研究的目的:
- 调查SOX11在调节MCL中氧化应激和氧化还原平衡中的作用.
- 探索SOX11,活性氧物种 (ROS) 和MCL中的PRDX2表达之间的关系.
- 评估向PRDX2在侵袭性MCL中的治疗潜力.
主要方法:
- 独立的MCL患者系列的基因组丰富分析.
- 在SOX11+与SOX11-MCL瘤中分析ROS度和PRDX2表达.
- 在MCL细胞系中进行的SOX11淘汰 (SOX11KO) 和PRDX2淘汰 (PRDX2KD) 实验.
- 在药物治疗后对ROS介导的细胞死亡的评估.
主要成果:
- 与SOX11- MCL相比,SOX11+ MCL瘤呈现出更高的ROS水平和增加的PRDX2表达.
- PRDX2上调与SOX11过度表达,较高的ROS和较差的患者存活率显著相关.
- SOX11KO减少了PRDX2的表达,而SOX11KO和PRDX2KD增加了ROS和ROS介导的细胞死亡.
- 通过SOX11介导的PRDX2上调调节的异常还原稳定作用与MCL化学抵抗有关.
结论:
- SOX11通过上调PRDX2.2.来调节MCL中的氧化还原稳定作用.
- 这种SOX11-PRDX2轴有助于增加ROS水平和激进的MCL中的化学抵抗.
- PRDX2代表了一个潜在的治疗点,用于克服激进的MCL中的化疗抵抗.
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