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Long Noncoding RNA DRAIC Inhibits Prostate Cancer Progression by Interacting with IKK to Inhibit NF-κB Activation.
Cancer Research ( IF 12.5 ) Pub Date : 2020-01-03 , DOI: 10.1158/0008-5472.can-19-3460
Shekhar Saha 1 , Manjari Kiran 1 , Canan Kuscu 1 , Ajay Chatrath 1 , David Wotton 1 , Marty W Mayo 1 , Anindya Dutta 1
Affiliation  

DRAIC is a 1.7 kb spliced long noncoding RNA downregulated in castration-resistant advanced prostate cancer. Decreased DRAIC expression predicts poor patient outcome in prostate and seven other cancers, while increased DRAIC represses growth of xenografted tumors. Here, we show that cancers with decreased DRAIC expression have increased NF-κB target gene expression. DRAIC downregulation increased cell invasion and soft agar colony formation; this was dependent on NF-κB activation. DRAIC interacted with subunits of the IκB kinase (IKK) complex to inhibit their interaction with each other, the phosphorylation of IκBα, and the activation of NF-κB. These functions of DRAIC mapped to the same fragment containing bases 701-905. Thus, DRAIC lncRNA inhibits prostate cancer progression through suppression of NF-κB activation by interfering with IKK activity. SIGNIFICANCE: A cytoplasmic tumor-suppressive lncRNA interacts with and inhibits a major kinase that activates an oncogenic transcription factor in prostate cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/950/F1.large.jpg.

中文翻译:

长非编码RNA DRAIC通过与IKK相互作用抑制NF-κB活化来抑制前列腺癌的进展。

DRAIC是在去势抵抗性晚期前列腺癌中下调的1.7 kb剪接长非编码RNA。DRAIC表达降低预示着前列腺癌和其他七种癌症的患者预后不良,而DRAIC升高则抑制异种移植肿瘤的生长。在这里,我们显示DRAIC表达降低的癌症的NF-κB靶基因表达增加。DRAIC下调增加细胞侵袭和软琼脂集落的形成;这取决于NF-κB的激活。DRAIC与IκB激酶(IKK)复合体的亚基相互作用,以抑制它们之间的相互作用,IκBα的磷酸化以及NF-κB的激活。DRAIC的这些功能映射到包含碱基701-905的同一片段。从而,DRAIC lncRNA通过干扰IKK活性来抑制NF-κB活化,从而抑制前列腺癌的进展。意义:细胞质肿瘤抑制性lncRNA与前列腺癌相互作用并抑制其激活致癌转录因子的主要激酶。图形摘要:http://cancerres.aacrjournals.org/content/canres/80/5/950/F1.large.jpg。
更新日期:2020-03-02
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