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Hypoxia‐sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR‐30a‐3p in non‐small cell lung cancer

Authors :
Shuai Yuan
Ying Xiang
Guilu Wang
Meiyu Zhou
Gang Meng
Qingyun Liu
Zeyao Hu
Chengying Li
Weijia Xie
Na Wu
Long Wu
Tongjian Cai
Xiangyu Ma
Yao Zhang
Zubin Yu
Li Bai
Yafei Li
Source :
Molecular Oncology, Vol 13, Iss 4, Pp 840-856 (2019)
Publication Year :
2019
Publisher :
Wiley, 2019.

Abstract

Dysregulation of long noncoding RNA (lncRNA) is known to be involved in numerous human diseases, including lung cancer. However, the precise biological functions of most lncRNA remain to be elucidated. Here, we identified a novel up‐regulated lncRNA, LINC01436 (RefSeq: NR_110419.1), in non‐small cell lung cancer (NSCLC). High expression of LINC01436 was significantly associated with poor overall survival. Notably, LINC01436 expression was transcriptionally repressed by E2F6 under normoxia, and the inhibitory effect was relieved in a hypoxic microenvironment. Gain‐ and loss‐of‐function studies revealed that LINC01436 acted as a proto‐oncogene by promoting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays in nude mice confirmed that LINC01436 promoted tumor growth and metastasis in vivo. Mechanistically, LINC01436 exerted biological functions by acting as a microRNA (miR)‐30a‐3p sponge to regulate the expression of its target gene EPAS1. Our findings characterize LINC01436 as a new hypoxia‐sensitive lncRNA with oncogenic function in NSCLC, suggesting that LINC01436 may be a potential biomarker for prognosis and a potential target for treatment.

Details

Language :
English
ISSN :
18780261 and 15747891
Volume :
13
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Molecular Oncology
Publication Type :
Academic Journal
Accession number :
edsdoj.2be4dc7e5cec4e209824731314216f04
Document Type :
article
Full Text :
https://doi.org/10.1002/1878-0261.12437