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 |
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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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