Oncotarget

Research Papers:

The pseudogene DUXAP10 promotes an aggressive phenotype through binding with LSD1 and repressing LATS2 and RRAD in non small cell lung cancer

Chen-Chen Wei _, Feng-Qi Nie, Li-Li Jiang, Qin-Nan Chen, Zhen-Yao Chen, Xin Chen, Xuan Pan, Zhi-Li Liu, Bin-Bin Lu and Zhao-Xia Wang

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:5233-5246. https://doi.org/10.18632/oncotarget.14125

Metrics: PDF 907 views  |   HTML 1610 views  |   ?  


Abstract

Chen-Chen Wei1,*, Feng-Qi Nie1,*, Li-Li Jiang1,2,*, Qin-Nan Chen1, Zhen-Yao Chen1, Xin Chen1, Xuan Pan3, Zhi-Li Liu4, Bin-Bin Lu1, Zhao-Xia Wang1

1Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China

2Department of Oncology, Haimen People’s Hospital, Haimen, People’s Republic of China

3Department of Medical Oncology, Nanjing Medical University Affiliated Cancer Hospital of Jiangsu Province, Cancer Institution of Jiangsu Province, Nanjing, People’s Republic of China

4Department of Oncology, The Affiliated Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, People’s Republic of China

*These authors contributed equally to this work and should be regarded as joint first authors

Correspondence to:

Zhao-Xia Wang, email: zhaoxiawang88@126.com

Keywords: pseudogene, DUXAP10, LSD1, proliferation, migration and invasion

Received: June 06, 2016    Accepted: November 21, 2016    Published: December 23, 2016

ABSTRACT

Pseudogenes have been considered as non-functional transcriptional relics of human genomic for long time. However, recent studies revealed that they play a plethora of roles in diverse physiological and pathological processes, especially in cancer, and many pseudogenes are transcribed into long noncoding RNAs and emerging as a novel class of lncRNAs. However, the biological roles and underlying mechanism of pseudogenes in the pathogenesis of non small cell lung cancer are still incompletely elucidated. This study identifies a putative oncogenic pseudogene DUXAP10 in NSCLC, which is located in 14q11.2 and 2398 nt in length. Firstly, we found that DUXAP10 was significantly up-regulated in 93 human NSCLC tissues and cell lines, and increased DUXAP10 was associated with patients poorer prognosis and short survival time. Furthermore, the loss and gain of functional studies including growth curves, migration, invasion assays and in vivo studies verify the oncogenic roles of DUXAP10 in NSCLC. Finally, the mechanistic experiments indicate that DUXAP10 could interact with Histone demethylase Lysine specific demethylase1 (LSD1) and repress tumor suppressors Large tumor suppressor 2 (LATS2) and Ras-related associated with diabetes (RRAD) transcription in NSCLC cells. Taken together, these findings demonstrate DUXAP10 exerts the oncogenic roles through binding with LSD1 and epigenetic silencing LATS2 and RRAD expression. Our investigation reveals the novel roles of pseudogene in NSCLC, which may serve as new target for NSCLC diagnosis and therapy.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 14125