Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies.

Long non-coding RNAs in hematological malignancies: translating basic techniques into diagnostic and therapeutic strategies.
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血液恶性肿瘤中的长非编码RNA:将基本技术转化为诊断和治疗策略

DOI:
10.1186/s13045-018-0673-6
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发表时间:
2018-11-22
影响因子:
28.5
通讯作者:
Yip SP
Yip SP
中科院分区:
医学1区
文献类型:
--
作者:
Wong NK;Huang CL;Islam R;Yip SP

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最近的研究表明,非编码区构成了人类基因组的绝大多数,长链非编码RNA(lncRNA)是一类涉及多种生物过程的非编码RNA。lncRNA的异常表达也与包括癌症在内的多种人类疾病有关,但lncRNA的调控机制和功能作用仍不明确,分子细节也需要证实。与蛋白质编码基因不同,lncRNA具有功能多样性和物种间保守性低等独特而复杂的特征,这极大地阻碍了lncRNA的实验研究。在这篇综述中,我们总结和讨论了传统的和先进的方法,识别和功能特性的lncRNA相关的血液恶性肿瘤。特别地,设想成簇规则间隔短回文重复序列(CRISPR)-Cas系统作为基因编辑工具的效用和进展,以促进通过不同敲入/敲除策略对lncRNA的分子解剖。除了lncRNA的实验考虑,lncRNA在白血病的发病机制和进展中的作用也突出了在审查中。我们预计这些见解最终可能导致临床应用,包括开发生物标志物和靶向lncRNA的新型治疗方法。
Recent studies have revealed that non-coding regions comprise the vast majority of the human genome and long non-coding RNAs (lncRNAs) are a diverse class of non-coding RNAs that has been implicated in a variety of biological processes. Abnormal expression of lncRNAs has also been linked to different human diseases including cancers, yet the regulatory mechanisms and functional effects of lncRNAs are still ambiguous, and the molecular details also need to be confirmed. Unlike protein-coding gene, it is much more challenging to unravel the roles of lncRNAs owing to their unique and complex features such as functional diversity and low conservation among species, which greatly hamper their experimental characterization. In this review, we summarize and discuss both conventional and advanced approaches for the identification and functional characterization of lncRNAs related to hematological malignancies. In particular, the utility and advancement of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system as gene-editing tools are envisioned to facilitate the molecular dissection of lncRNAs via different knock-in/out strategies. Besides experimental considerations specific to lncRNAs, the roles of lncRNAs in the pathogenesis and progression of leukemia are also highlighted in the review. We expect that these insights may ultimately lead to clinical applications including development of biomarkers and novel therapeutic approaches targeting lncRNAs.
通过LNA Gapmer ASO吸毒LNCRNA MALAT1抑制蛋白酶体亚基的基因表达,并触发抗多膜骨髓瘤活性。
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发表时间: 2008-07-01
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