Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells
Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells
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DOI：
10.1016/j.bbrc.2015.02.043
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发表时间：
2015-03-01
影响因子：
3.1
通讯作者：
Akiyama, Tetsu
中科院分区：
文献类型：
--
作者：
Sugimasa, Hironobu;Taniue, Kenzui;Akiyama, Tetsu
异质核核糖核蛋白K（hnRNP K）是一种参与转录、mRNA剪接、mRNA稳定和翻译的多功能蛋白。虽然hnRNP K已被认为在许多癌症的发展中发挥作用，但其在结直肠癌中的分子功能仍然难以捉摸。在这里，我们表明，hnRNP K在有丝分裂过程中起着重要的作用，在HCT 116结肠癌细胞。此外，我们表明，hnRNP K直接反式激活NUF 2基因，其产品是一个组成部分的NDC 80动粒复合物，这是已知的是一个稳定的纺锤体微管动粒附件的关键。此外，敲低hnRNP K和NUF 2均导致中期染色体排列失败，结肠癌细胞生长急剧下降。这些结果表明hnRNP K-NUF 2轴对结肠癌细胞的有丝分裂过程和增殖是重要的，并且该轴可能是结肠癌治疗的靶点。(C)2015 Elsevier Inc. All rights reserved.
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein involved in transcription, mRNA splicing, mRNA stabilization and translation. Although hnRNP K has been suggested to play a role in the development of many cancers, its molecular function in colorectal cancer has remained elusive. Here we show that hnRNP K plays an important role in the mitotic process in HCT116 colon cancer cells. Furthermore, we demonstrate that hnRNP K directly transactivates the NUF2 gene, the product of which is a component of the NDC80 kinetochore complex and which is known to be critical for a stable spindle microtubule-kinetochore attachment. In addition, knockdown of both hnRNP K and NUF2 caused failure in metaphase chromosome alignment and drastic decrease in the growth of colon cancer cells. These results suggest that the hnRNP K-NUF2 axis is important for the mitotic process and proliferation of colon cancer cells and that this axis could be a target for the therapy of colon cancer. (C) 2015 Elsevier Inc. All rights reserved.