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The long non-coding RNA HOTAIR increases tumour growth and invasion in cervical cancer by targeting the Notch pathway

Authors
 Maria Lee  ;  Hee Jung Kim  ;  Sang Wun Kim  ;  Sun-Ae Park  ;  Kyung-Hee Chun  ;  Nam Hoon Cho  ;  Yong Sang Song  ;  Young Tae Kim 
Citation
 ONCOTARGET, Vol.7(28) : 44558-44571, 2016 
Journal Title
ONCOTARGET
Issue Date
2016
MeSH
Adult ; Animals ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic* ; Humans ; Kaplan-Meier Estimate ; Magnetic Resonance Imaging ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Invasiveness ; Positron-Emission Tomography ; RNA, Long Noncoding/genetics* ; Receptors, Notch/genetics* ; Signal Transduction/genetics* ; Transplantation, Heterologous ; Tumor Burden/genetics ; Uterine Cervical Neoplasms/diagnostic imaging ; Uterine Cervical Neoplasms/genetics* ; Uterine Cervical Neoplasms/pathology
Keywords
HOTAIR ; cervical cancer ; invasion ; long non-coding RNA ; prognosis
Abstract
Evidence suggests that the long non-coding RNA (lncRNA), HOTAIR, is involved in cervical cancer pathogenesis. We examined serum HOTAIR expression levels in cervical cancer patients and determined the relationships between HOTAIR expression and several clinicopathological factors, including survival. We also examined the functional consequences of HOTAIR overexpression both in vitro and in vivo. Compared with control patients, HOTAIR expression was significantly greater in the serum of cervical cancer patients (P < 0.001). The results indicated that this increase was significantly associated with tumour size (P = 0.030), lymphovascular space invasion (P = 0.037), and lymph node metastasis (P = 0.043). Univariate analysis revealed that disease-free survival and overall survival times were significantly shorter in cervical cancer patients with high HOTAIR expression (hazard ratio [HR] = 4.27, 4.68 and P = 0.039, 0.031, respectively). Cell proliferation and invasion in vitro increased as a result of lentiviral-mediated HOTAIR overexpression in cervical cancer cell lines. HOTAIR knockdown inhibited these properties and increased apoptosis. In vivo xenograft experiments using the HOTAIR-overexpressing SiHa cell line revealed that HOTAIR was a strong inducer of tumour growth and modulated the expression of epithelial-mesenchymal transition and Notch-Wnt signalling pathway-related genes. This result suggested that HOTAIR overexpression promoted cell proliferation and invasion. In conclusion, increased HOTAIR expression was associated with decreased patient survival times. HOTAIR may be a useful target for treatment of cervical cancer patients.
Files in This Item:
T201602722.pdf Download
DOI
10.18632/oncotarget.10065
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151713
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