通过海绵化miR146a-5p和准NUMB,CircCRIM1可以抑制骨肉瘤的进展
Jinnan Chen1, Ruoxuan Hei1,2, Chen Chen1
1Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
American journal of cancer research
|September 11, 2023
概括
循环CRIM1 (circCRIM1) 在骨髓瘤 (OS) 中充当瘤抑制剂. 它通过菌miR146a-5p来抑制OS细胞的增殖,迁移和入侵,从而抑制瘤生长.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 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:
- 循环RNAs (circRNAs) 是瘤发生的新兴调节者.
- 在骨髓瘤 (OS) 进展中circCRIM1的作用仍然在很大程度上未被探索.
- 了解circRNA功能对于开发新型癌症疗法至关重要.
研究的目的:
- 研究circCRIM1在骨髓瘤 (OS) 中的作用和潜在机制.
- 为了确定circCRIM1是否在OS中充当瘤抑制剂或瘤基因.
- 阐明涉及OS中的circCRIM1,miRNA和目标基因的分子相互作用.
主要方法:
- 使用GSE96964数据集对OS细胞系中circRNAs的差异表达分析.
- 通过RT-qPCR和FISH测试,检查circCRIM1的表达和定位.
- 在体外 (细胞培养) 和体内 (裸体小鼠模型) 功能增益实验.
- 双露西法酶记者测定和生物信息预测,以识别miRNA海绵和目标基因.
主要成果:
- 在人类OS细胞系中,CircCRIM1显著下调,并在细胞质中局部化.
- 过度表达circCRIM1抑制了OS细胞的增殖,迁移和入侵在体外,并在体内抑制了瘤的生长.
- 循环CRIM1直接菌miR146a-5p,导致其下游目标NUMB的表达增加,并抑制了Notch信号通路.
- 过度表达MiR146a-5p逆转了OS细胞中circCRIM1的瘤抑制作用.
结论:
- 在骨髓瘤中,CircCRIM1作为瘤抑制剂起作用.
- 该circCRIM1/miR-146a-5p/NUMB轴通过调节Notch信号通路来调节OS进展.
- CircCRIM1代表了骨髓瘤治疗的潜在治疗标.
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