循环RNA驱动在白血病中MLL复合体内的瘤性染色体转位
Vanessa M Conn1, Marta Gabryelska2, John Toubia3
1Flinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia; Centre for Cancer Biology, SA Pathology & University of South Australia, Adelaide, SA 5000, Australia.
Cancer cell
|June 9, 2023
概括
循环RNAs (circRNAs) 结合DNA形成circR循环,促进导致白血病的遗传突变. 这些RNA分子在小鼠中的过度表达加速了疾病的发病,并产生了与癌症相关的染色体转位.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
背景情况:
- 瘤发生,癌症的开始,需要遗传突变.
- 染色体转位涉及MLL基因,在急性白血病 (MLL复合体) 中形成瘤基因.
研究的目的:
- 研究圆形RNAs (circRNAs) 在MLL复合体形成和白血病发生中的作用.
- 确定circRNA是否可以诱导染色体转位.
主要方法:
- 在MLL复合体中分析circRNA丰富.
- 生物化学分析检测circRNA:DNA杂交物 (circR循环).
- 在体内研究使用鼠标白血病异种移植模型与circRNA过度表达.
主要成果:
- 在MLL复合体中,circRNAs被丰富,并在相似的DNA位置形成circR循环.
- circR循环诱导转录暂停,蛋白酶体抑制,染色体变化和DNA断裂.
- 在小鼠中,circRNAs的过度表达导致了基因组位点的共同定位,新的染色体转位,以及更快的疾病进展.
结论:
- 内源性circRNAs可以通过诱导染色体转位来作为RNA致癌物.
- circR循环是一种新的机制,有助于白血病中观察到的遗传不稳定性.
- 这项研究揭示了由RNA分子驱动的瘤发生的新途径.
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