抑制MiR-34c-5p会影响Bax/Bcl2的表达,并逆转多发性髓瘤细胞中的博特佐米布抗性
Emad Matour1,2, Zari Tahannejad Asadi1,2, Ahmad Ahmadzadeh Deilami3
1Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jondishapur University of Medical Sciences, Ahvaz, Iran.
概括
多发性骨髓瘤 (MM) 的耐药性是一个主要的挑战. 这项研究发现,抑制microRNA-34c-5p (miR-34c-5p) 通过影响细胞亡来重新敏感化抗博特佐米布的MM细胞,这提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 对抗癌药物,特别是酶体抑制剂 (如博尔特佐米布) 的耐药性显著复杂化了多发性骨髓瘤 (MM) 的治疗.
- 展开的蛋白质反应 (UPR) 和微RNA (miRNA) 已与MM的耐药性发展有关.
- 了解miRNAs在中介抗性的特定作用对于开发新型治疗策略至关重要.
研究的目的:
- 为了研究X-box结合蛋白1 (XBP1) 和特定的miRNAs (hsa-miR-34c-5p,hsa-miR-214,hsa-miR-30c-2*) 在对博特佐米布敏感和抵抗博特佐米布的多发性髓瘤细胞系中的表达特征.
- 为了确定调节hsa-miR-34c-5p表达对与亡相关的蛋白质 (Bax/Bcl-2) 的作用,并克服MM细胞中的博特佐米布耐药性.
主要方法:
- 建立抗博特佐米布的多发性髓瘤细胞系.
- 定量实时PCR (qRT-PCR) 用于评估XBP1,hsa-miR-34c-5p,hsa-miR-214和hsa-miR-30c-2*的表达水平.
- 抑制hsa-miR-34c-5p以评估其对Bax和Bcl-2表达的影响.
- MTT测定以确认药物耐药性.
- 使用t测试进行统计分析.
主要成果:
- 在敏感和耐药的MM细胞系之间观察到XBP1和hsa-miR-34c-5p表达的显著差异.
- 在耐药细胞中抑制hsa-miR-34c-5p导致Bax表达增加和Bcl-2表达减少.
- 抑制hsa-miR-34c-5p成功地使抗博特佐米布的MM细胞对博特佐米布治疗重新敏感.
- 通过hsa-miR-34c-5p对Bax/Bcl-2表达的调节被确定为克服耐药性的关键机制.
结论:
- Hsa-miR-34c-5p在对博尔特佐米布敏感的多发性骨髓瘤细胞和对抗性多发性骨髓瘤细胞中表达不同.
- 抑制hsa-miR-34c-5p可以通过通过Bax/Bcl-2通路调节亡来克服MM中的博特佐米布耐药性.
- Hsa-miR-34c-5p代表了在多发性髓瘤中克服蛋白酶体抑制剂耐药性的潜在治疗标.
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