Oncotarget

Research Papers:

DDX23-Linc00630-HDAC1 axis activates the Notch pathway to promote metastasis

Guozhang Mao _, Hui Jin and Liuguang Wu

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Oncotarget. 2017; 8:38937-38949. https://doi.org/10.18632/oncotarget.17156

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Abstract

Guozhang Mao1, Hui Jin1, Liuguang Wu1

1Department of Cardio-Thoracic Surgery, Zhoukou Center Hospital of Henan Province, Henan 466000, China

Correspondence to:

Guozhang Mao, email: guozhangmaoch@163.com

Keywords: Linc00630, HDAC1, DDX23, Notch signaling pathway, NSCLC

Received: February 02, 2017     Accepted: April 03, 2017     Published: April 17, 2017

ABSTRACT

Emerging studies demonstrated the roles of long non-coding RNAs (LncRNAs) are being implicated in the progression of many cancers. Here we report the discovery of a critical role for the linc00630 in the development of Non-Small-Cell Lung Cancers (NSCLCs). Screening from the microarray of six paired NSCLCs and adjacent non-tumor tissues, linc00630 showed a significantly higher RNA levels in NSCLCs. With the higher level confirmed in a separate cohort 90 NSCLCs patients, overexpressed of linc00630 also positive associated with tumor size, TNM tumor stage, lymph node status positive and overall patient outcomes. Linc00630 overexpression increased cell proliferation and metastasis in vitro and in vivo whereas linc00630 silencing had opposite effects. By RNA pull-down and mass spectrometry we identified Histone deacetylases 1 (HDAC1) and DEAD-box helicase 23 (DDX23) as the linc00630-binding protein that associated with mechanism of linc00630. DDX23 can specific bind with the promoter of Linc00630 to up-regulate the RNA level and high level of linc00630 strength the protein stability of HDAC1 to regulate the downstream pathway.

Our study demonstrates the effectiveness of Linc00630 oligonucleotide-based promotion of NSCLCs metastasis and proliferation, illuminating a new basis of DDX23-Linc00630-HDAC1 signal axis for understanding its pathogenicity, which could be further developed as a valuable therapeutic strategy.


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