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

Autor: Gang Meng, Chengying Li, Meiyu Zhou, Qingyun Liu, Zeyao Hu, Weijia Xie, Long Wu, Zubin Yu, Xiangyu Ma, Na Wu, Tong-Jian Cai, Yafei Li, Li Bai, Ying Xiang, Yao Zhang, Guilu Wang, Shuai Yuan
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Lung Neoplasms
E2F6 Transcription Factor
Proto-Oncogene Mas
Metastasis
0302 clinical medicine
Cell Movement
Carcinoma
Non-Small-Cell Lung
Basic Helix-Loop-Helix Transcription Factors
Neoplasm Metastasis
Research Articles
Mice
Inbred BALB C
EPAS1
General Medicine
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Long non-coding RNA
Up-Regulation
Gene Expression Regulation
Neoplastic
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
RNA
Long Noncoding
Research Article
non‐small cell lung cancer
Mice
Nude
Biology
lcsh:RC254-282
Models
Biological
03 medical and health sciences
In vivo
Cell Line
Tumor
microRNA
Genetics
medicine
Animals
Humans
Neoplasm Invasiveness
long noncoding RNA
Lung cancer
Cell Proliferation
microRNA‐30a‐3p
Oncogene
Base Sequence
hypoxia
Oncogenes
LINC01436
medicine.disease
Survival Analysis
In vitro
MicroRNAs
030104 developmental biology
Cancer research
Tumor Hypoxia
Zdroj: Molecular Oncology
Molecular Oncology, Vol 13, Iss 4, Pp 840-856 (2019)
ISSN: 1878-0261
1574-7891
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: OpenAIRE
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