长链非编码RNA CRNDE稳定SIRT1蛋白并影响多发性骨髓瘤中的刺猬信号传导

IF 13.4 1区 医学 Q1 HEMATOLOGY
Simone Zocchi, Pauline Trichet, Paloma Guernalec, Manal Agdada, Ana Alonso Bartolomé, Vincent Ogor, Caroline Choisy, Carine Vias, Xavier Sabaté-Cadenas, Jean-Christophe Bories, Michele Goodhardt, Alena Shkumatava, David Garrick
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引用次数: 0

摘要

多发性骨髓瘤(MM)是一种免疫球蛋白分泌浆细胞的恶性肿瘤,占所有血液学癌症的10%,尽管最近取得了进展,但基本上仍然无法治愈。长链非编码rna (lncRNAs)是一类重要的调控分子,与MM的病因密切相关。结直肠癌差异表达(CRNDE)是MM患者肿瘤浆细胞中上调的一种lncRNA,有助于疾病的进展和结局。为了表征CRNDE在MM中的作用的分子机制,我们进行了高通量筛选,以鉴定细胞内与该lncRNA相互作用的蛋白质。从这个屏幕的输出,我们证明了在MM细胞中,CRNDE与脱乙酰酶蛋白SIRT1相互作用并稳定,SIRT1先前被认为是MM中Hedgehog (Hh)信号通路的重要介质。我们进一步表明,CRNDE通过对SIRT1/Hh信号轴的影响,对MM细胞存活、致瘤潜力和茎样特性产生下游影响。我们的发现增加了对CRNDE在MM中的致瘤活性的分子理解,并可能在其他恶性疾病中具有更广泛的意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The long non-coding RNA CRNDE stabilises SIRT1 protein and influences Hedgehog signalling in multiple myeloma

The long non-coding RNA CRNDE stabilises SIRT1 protein and influences Hedgehog signalling in multiple myeloma

Multiple myeloma (MM) is a malignancy of immunoglobulin-secreting plasma cells that represents 10% of all hematological cancers and remains essentially incurable, despite recent advances. Long non-coding RNAs (lncRNAs) are an important class of regulatory molecules that have been strongly implicated in the aetiology of MM. Colorectal Neoplasia Differentially Expressed (CRNDE) is one lncRNA that is upregulated in tumor plasma cells of MM patients and contributes to disease progression and outcome. In order to characterise the molecular mechanisms of CRNDE action in MM, here we have carried out a high-throughput screen to identify proteins interacting with this lncRNA inside cells. From the output of this screen, we demonstrate that in MM cells, CRNDE interacts with and stabilises the deacetylase protein SIRT1, previously identified as an important mediator of the Hedgehog (Hh) signalling pathway in MM. We further show that CRNDE exerts downstream effects on MM cell survival, tumorigenic potential, and stem-like properties via an effect on the SIRT1/Hh signalling axis. Our findings add to the molecular understanding of the pro-tumorigenic activity of CRNDE in MM and could have wider implications in other malignant diseases.

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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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