Oncotarget

Research Papers:

Downregulation of long non-coding RNA LET predicts poor prognosis and increases Notch signaling in non-small cell lung cancer

Shengwen Li, Hui Zhao, Jianqiang Li _, Aizheng Zhang and Haibin Wang

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Oncotarget. 2018; 9:1156-1168. https://doi.org/10.18632/oncotarget.23452

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Abstract

Shengwen Li1,2,3, Hui Zhao2, Jianqiang Li2, Aizheng Zhang3 and Haibin Wang3,4

1Shanxi Medical University, Taiyuan, Shanxi 030001, China

2Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China

3Department of Respiratory and Critical Medicine, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030012, China

4Division of Allergy and Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

Correspondence to:

Jianqiang Li, email: [email protected]

Haibin Wang, email: [email protected]

Keywords: long non-coding RNA-LET; NSCLC; prognosis; Notch signaling

Abbreviations: NSCLC: non-small cell lung cancer; lncRNA: long non-coding RNA; lncRNA-LET: lncRNA low expression in tumor; Notch signaling, Notch1 intracellular domain (NICD1)

Received: June 23, 2017    Accepted: December 09, 2017    Published: December 19, 2017

ABSTRACT

Long non-coding RNAs (lncRNAs) have been found to be dysregulated in a variety of tumors. The lncRNA-Low Expression in Tumor (LET) is a recently identified lncRNA, but its expression pattern and biological significance in human non-small cell lung cancer (NSCLC) are still largely unknown. In this study, we found that lncRNA-LET was significantly downregulated in human NSCLC lung tissues and cell lines. Decreased lncRNA-LET expression was strongly associated with advanced tumor stages and poorer overall survival of NSCLC patients. Functionally, overexpression of lncRNA-LET in NSCLC H292 cells significantly suppressed cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis, while knockdown of lncRNA-LET in NSCLC H1975 cells showed an opposite effect, pointing to a tumor-suppressive role for lncRNA-LET in NSCLC. Mechanistically, we demonstrated that lncRNA-LET overexpression significantly reduced the expression of Notch1 intracellular Domain (NICD1) in H292 cells while knockdown of lncRNA-LET increased NICD1 expression in H1975 cells. Similarly, NSCLC lung tissues with high levels of lncRNA-LET had lower NICD1 expression. Thus, our results provide a strong rationale for lncRNA-LET to be used as a prognostic indicator and a potent therapeutic target for NSCLC patients, and highlight a novel lncRNA-LET/Notch axis in regulating NSCLC cell fate and tumor progression.


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