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ZCCHC4通过ROS/c-myc轴调节食道癌的进展和对西斯普拉丁的耐药性
Lihua Yao1,2, Piao Wu1, Fangyi Yao2
1Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, School of Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
Scientific reports
|February 11, 2025
概括
低调指CCHC类型含有4 (ZCCHC4) 增强食道癌细胞对西斯普拉丁的敏感性,抑制增殖,并通过ROS/c-myc轴促进细胞亡. 这表明ZCCHC4是食道癌的潜在诊断和治疗标.
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:
- 指CCHC类型含有4 (ZCCHC4) 是一种N6-甲基氨酸RNA甲基转移酶,涉及各种癌症.
- 它在食道癌 (ESCA) 中的作用仍然在很大程度上未被描述.
- 异常ZCCHC4表达与其他恶性瘤的不良预后和化学抵抗有关.
研究的目的:
- 研究食道癌中ZCCHC4的表达和功能作用.
- 确定ESCA患者中ZCCHC4表达和临床参数之间的关联.
- 阐明ZCCHC4对ESCA进展和西斯普拉丁耐药性的影响的潜在机制.
主要方法:
- 定量实时PCR (qRT-PCR) 和西布洛特用于ZCCHC4表达分析.
- 电化学发光免疫测试用于血清瘤标志物.
- 细胞增殖,细胞循环和细胞亡测定 (CCK8,流细胞计).
- 在小鼠模型中的体内研究.
主要成果:
- 在ESCA中,ZCCHC4表达与晚期癌症,淋巴结转移和较差的整体存活率有关.
- ZCCHC4 mRNA水平与血清瘤标志物 (CEA,SCC,TPA) 相相关.
- ZCCHC4 Knockdown增加了西斯的敏感性,诱导了DNA损伤,提高了活性氧物种 (ROS),触发了S相停止,增强了亡,并抑制了增殖.
- 过度表达ZCCHC4具有相反的效果,促进增殖和化学抵抗.
- 降低ZCCHC4的调节抑制了瘤的进展和在体内对西斯普拉丁的耐药性,可能通过ROS/c-myc轴.
结论:
- 降低ZCCHC4的调节使食道癌细胞对西斯普拉丁敏感,抑制增殖,并促进亡.
- ZCCHC4在ESCA的进展和化学抵抗中发挥着重要作用.
- ZCCHC4代表了一个潜在的辅助生物标志物用于诊断和治疗目标在食道癌症.
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