研究动态
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转座子 DNA 序列促进循环肿瘤 DNA 在人类细胞之间进行组织特异性基因转移。

Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

发表日期:2024 May 23
作者: Munevver Cinar, Lourdes Martinez-Medina, Pavan K Puvvula, Arsen Arakelyan, Badri N Vardarajan, Neil Anthony, Ganji P Nagaraju, Dongkyoo Park, Lei Feng, Faith Sheff, Marina Mosunjac, Debra Saxe, Steven Flygare, Olatunji B Alese, Jonathan L Kaufman, Sagar Lonial, Juan M Sarmiento, Izidore S Lossos, Paula M Vertino, Jose A Lopez, Bassel El-Rayes, Leon Bernal-Mizrachi
来源: NUCLEIC ACIDS RESEARCH

摘要:

已知细胞之间的基因交换在许多生物体中发挥重要的生理和病理作用。我们证明循环肿瘤 DNA (ctDNA) 促进人类癌细胞之间的细胞特异性基因转移,并解释了这种现象背后的部分机制。当 ctDNA 迁移到细胞核中时,遗传信息就会被转移。细胞靶向和 ctDNA 整合需要 ERVL、SINE 或 LINE DNA 序列。化学制造的 AluSp 和 MER11C 序列复制了多发性骨髓瘤 (MM) ctDNA 细胞靶向和整合。此外,我们发现 ctDNA 可能会改变 MM 和胰腺癌模型的治疗反应。这项研究表明逆转录转座子 DNA 序列促进癌症基因转移。然而,由于在生理和其他病理条件下都检测到了游离 DNA,因此我们的研究结果不仅具有癌症的影响,而且具有更广泛的影响。此外,转座子 DNA 序列介导组织特异性靶向的发现将为基因和疗法的传递开辟新途径。© 作者 2024。由牛津大学出版社代表 Nucleic Acids Research 出版。
The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicated multiple myeloma (MM) ctDNA cell targeting and integration. Additionally, we found that ctDNA may alter the treatment response of MM and pancreatic cancer models. This study shows that retrotransposon DNA sequences promote cancer gene transfer. However, because cell-free DNA has been detected in physiological and other pathological conditions, our findings have a broader impact than just cancer. Furthermore, the discovery that transposon DNA sequences mediate tissue-specific targeting will open up a new avenue for the delivery of genes and therapies.© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.