在基诱导的恶性TK6细胞中,DNMT1调节过甲基化和静止hsa_circ_401351
Yali Han1,2, Jinxue Meng1,2, Xiaoxuan Ling1
1Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, People's Republic of China.
Environmental toxicology
|December 18, 2023
概括
氨酸 (HQ) 暴露会降低循环RNA (circRNA) hsa_circ_401351的表达,促进急性髓性白血病 (AML) 细胞生长. 恢复 hsa_circ_401351 的表达抑制了 HQ 诱导的 AML 细胞的增殖并增强了 AML 细胞的亡.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 及其代谢物化 (HQ) 与急性髓性白血病 (AML) 的发展有关.
- 循环RNAs (circRNAs) 与白血病有关,但它们的特定作用和调节机制尚不清楚.
研究的目的:
- 为了研究hsa_circ_401351在氨酸诱导的AML中的作用.
- 阐明 AML 中hsa_circ_401351 失调的分子机制.
主要方法:
- 使用的细胞模型包括基诱导的TK6细胞 (HQ-TK6).
- 通过qRT-PCR评估hsa_circ_401351表达和通过甲基化特异PCR进行促剂甲基化.
- 通过使用CRISPR/Cas9敲击,研究了DNA甲基转移酶 (DNMT1,DNMT3b) 的作用.
- 在hsa_circ_401351过度表达后,使用CCK-8试验和流细胞计分析了细胞增殖和细胞亡.
主要成果:
- 与对照组相比,HQ-TK6细胞表现出明显较低的hsa_circ_401351表达.
- 基因组甲基转移酶抑制剂 (5-AzaC,TSA) 和DNMT1倒置增加了hsa_circ_401351的表达,并降低了促进物甲基化.
- 在HQ-TK6细胞中hsa_circ_401351的过度表达抑制了增殖,诱导了G1阶段停止和增强了亡.
- 在hsa_circ_401351过度表达后,观察到减少的Caspase-3和升高的Bcl-2水平.
结论:
- 在HQ-TK6细胞中DNMT1表达的升高通过促进物高甲基化导致hsa_circ_401351表达的降低.
- hsa_circ_401351通过抑制HQ诱导的AML的增殖和促进亡,作为瘤抑制剂.
- 针对DNMT1或恢复hsa_circ_401351的表达可能为AML提供治疗策略.
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