Abstract：
BACKGROUND: α-Crystallin B (CRYAB) is a chaperone member of the HSPs family that protects proteins with which it interacts from degradation. This study aims to investigate the effect of CRYAB on the progression of colorectal cancer (CRC) and its underlying mechanism.
METHODS: CRYAB expression was evaluated in CRC tissues. Cell growth was tested by CCK-8 kit. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays were used to assess the degree of cellular lipid peroxidation of CRC cells. The potential signal pathways of CRYAB were analyzed and verified by Western blot (WB) and immunoprecipitation (Co-IP).
RESULTS: CRYAB expression was elevated in CRC tissues and exhibited sensitivity and specificity in predicting CRC. Functionally, knockdown of CRYAB induced ferroptosis in CRC cells. Mechanistically, CRYAB binding prevented from β-catenin interacting with TRIM55, leading to an increase in β-catenin protein stability, which desensitized CRC cells to ferroptosis and ultimately accelerated cancer progression.
CONCLUSIONS: Targeting CRYAB might be a promising strategy to enhance ferroptosis and improve the efficacy of CRC therapy.
METHODS: CRYAB expression was evaluated in CRC tissues. Cell growth was tested by CCK-8 kit. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays were used to assess the degree of cellular lipid peroxidation of CRC cells. The potential signal pathways of CRYAB were analyzed and verified by Western blot (WB) and immunoprecipitation (Co-IP).
RESULTS: CRYAB expression was elevated in CRC tissues and exhibited sensitivity and specificity in predicting CRC. Functionally, knockdown of CRYAB induced ferroptosis in CRC cells. Mechanistically, CRYAB binding prevented from β-catenin interacting with TRIM55, leading to an increase in β-catenin protein stability, which desensitized CRC cells to ferroptosis and ultimately accelerated cancer progression.
CONCLUSIONS: Targeting CRYAB might be a promising strategy to enhance ferroptosis and improve the efficacy of CRC therapy.
摘要：
背景：α-晶体蛋白B（CRYAB）是HSPs家族的伴侣成员，可保护与其相互作用的蛋白质免于降解。本研究旨在探讨CRYAB对结直肠癌(CRC)进展的影响及其机制。
方法：在CRC组织中评估CRYAB的表达。通过CCK-8试剂盒测试细胞生长。脂质活性氧（ROS）测定，脂质过氧化测定，谷胱甘肽测定用于评估CRC细胞的细胞脂质过氧化程度。通过Westernblot（WB）和免疫沉淀（Co-IP）分析和验证CRYAB的潜在信号通路。
结果：CRYAB在CRC组织中表达升高，在预测CRC时表现出敏感性和特异性。功能上,CRYAB敲低诱导CRC细胞中的铁凋亡。机械上,CRYAB结合阻止β-catenin与TRIM55相互作用，导致β-catenin蛋白稳定性增加，它使CRC细胞对铁凋亡脱敏并最终加速癌症进展。
结论：靶向CRYAB可能是一种有希望的策略，以增强铁细胞凋亡并提高CRC治疗的疗效。
方法：在CRC组织中评估CRYAB的表达。通过CCK-8试剂盒测试细胞生长。脂质活性氧（ROS）测定，脂质过氧化测定，谷胱甘肽测定用于评估CRC细胞的细胞脂质过氧化程度。通过Westernblot（WB）和免疫沉淀（Co-IP）分析和验证CRYAB的潜在信号通路。
结果：CRYAB在CRC组织中表达升高，在预测CRC时表现出敏感性和特异性。功能上,CRYAB敲低诱导CRC细胞中的铁凋亡。机械上,CRYAB结合阻止β-catenin与TRIM55相互作用，导致β-catenin蛋白稳定性增加，它使CRC细胞对铁凋亡脱敏并最终加速癌症进展。
结论：靶向CRYAB可能是一种有希望的策略，以增强铁细胞凋亡并提高CRC治疗的疗效。
