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

Autor: 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
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Molecular Oncology, Vol 13, Iss 4, Pp 840-856 (2019)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.12437
Popis: 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.
Databáze: Directory of Open Access Journals
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