NDLI: Long noncoding RNA HOTAIR, a hypoxia-inducible factor-1α activated driver of malignancy, enhances hypoxic cancer cell proliferation, migration, and invasion in non-small cell lung cancer

Content Provider	Springer Nature Link
Author	Zhou, Chunxia Ye, Lincai Jiang, Chuan Bai, Jie Chi, Yongbin Zhang, Haibo
Copyright Year	2015
Abstract	Despite the fact that great advances have been made in the management of non-small cell lung cancer (NSCLC), the prognosis of advanced NSCLC remains very poor. HOX transcript antisense intergenic RNA (HOTAIR) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in the progression of a variety of carcinomas and acts as a negative prognostic biomarker. Yet, little is known about the effect of HOTAIR in the hypoxic microenvironment of NSCLC. The expression and promoter activity of HOTAIR were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The function of the hypoxia-inducible factor-1α (HIF-1α) binding site to hypoxia-responsive elements (HREs) in the HOTAIR promoter region was tested by luciferase reporter assay with nucleotide substitutions. The binding of HIF-1α to the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay (CHIP) and electrophoretic mobility shift assay (EMSA). The effect of HIF-1α suppression by small interference RNA or YC-1 on HOTAIR expression was also determined. In the present study, we demonstrated that HOTAIR was upregulated by hypoxia in NSCLC cells. HOTAIR is a direct target of HIF-1α through interaction with putative HREs in the upstream region of HOTAIR in NSCLC cells. Furthermore, HIF-1α knockdown or inhibition could prevent HOTAIR upregulation under hypoxic conditions. Under hypoxic conditions, HOTAIR enhanced cancer cell proliferation, migration, and invasion. These data suggested that suppression of HOTAIR upon hypoxia of NSCLC could be a novel therapeutic strategy.
Starting Page	9179
Ending Page	9188
Page Count	10
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	36
Issue Number	12
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-06-19
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Non-small cell lung cancer Long noncoding RNA HOTAIR Hypoxia HIF-1α Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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