An antisense RNA capable of modulating the expression of the tumor suppressor microRNA-34a.

An antisense RNA capable of modulating the expression of the tumor suppressor microRNA-34a.
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DOI:
10.1038/s41419-018-0777-5
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发表时间:
2018-07-03
影响因子:
9
通讯作者:
Pokrovskaja Tamm K
Pokrovskaja Tamm K
中科院分区:
生物学1区
文献类型:
--
作者:
Serviss JT;Andrews N;Van den Eynden J;Richter FC;Houtman M;Vesterlund M;Schwarzmueller L;Johnsson P;Larsson E;Grandér D;Pokrovskaja Tamm K

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microRNA-34 a是一种研究充分的肿瘤抑制microRNA(miRNA),是TP 53的直接下游靶点,在与肿瘤发生相关的几种途径中发挥作用,如增殖、细胞生长和分化。由于其广泛的肿瘤抑制活性,miR 34 a表达在多种实体瘤和血液恶性肿瘤中改变并不令人惊讶。然而,miR 34 a在这些癌症中的调节机制在很大程度上是未知的。在这项研究中,我们发现一个长的非编码RNA转录反义的miR 34 a宿主基因,是至关重要的miR 34 a的表达和介导的细胞功能,在多种类型的人类癌症。我们将这种长的非编码RNA命名为lncTAM 34 a,并表征其在TP 53缺陷和野生型环境中不同类型的细胞应激下促进miR 34 a表达的能力。
The microRNA-34a is a well-studied tumor suppressor microRNA (miRNA) and a direct downstream target of TP53 with roles in several pathways associated with oncogenesis, such as proliferation, cellular growth, and differentiation. Due to its broad tumor suppressive activity, it is not surprising that miR34a expression is altered in a wide variety of solid tumors and hematological malignancies. However, the mechanisms by which miR34a is regulated in these cancers is largely unknown. In this study, we find that a long noncoding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer. We name this long noncoding RNA lncTAM34a, and characterize its ability to facilitate miR34a expression under different types of cellular stress in both TP53-deficient and wild-type settings.
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