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The long noncoding RNA HOXA11 antisense induces tumor progression and stemness maintenance in cervical cancer

Authors
Kim, Hee JungEoh, Kyung JinKim, Lee KyungNam, Eun JiYoon, Sun OchKim, Kun-HongLee, Jae KwanKim, Sang WunKim, Young Tae
Issue Date
13-12월-2016
Publisher
IMPACT JOURNALS LLC
Keywords
HOXA11 antisense; long noncoding RNA; invasion; prognosis; cervical cancer
Citation
ONCOTARGET, v.7, no.50, pp.83001 - 83016
Indexed
SCIE
SCOPUS
Journal Title
ONCOTARGET
Volume
7
Number
50
Start Page
83001
End Page
83016
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/86547
DOI
10.18632/oncotarget.12863
ISSN
1949-2553
Abstract
Recent research has focused on the impact of long noncoding RNA (lncRNA) in cervical carcinogenesis. However, whether HOXA11 antisense (HOXA11-AS) is involved in cervical cancer remains to be elucidated. In the present study, we examined HOXA11-AS expression levels in cervical cancer patients and determined the relationships between HOXA11-AS expression and clinicopathological factors. We also investigated the bio-functional consequences of HOXA11-AS overexpression both in vitro and in vivo. HOXA11-AS expression was significantly greater in tissues from patients with cervical cancer than in control patients (P< 0.001). Multivariate analysis showed that high HOXA11-AS was an independent prognosticator of overall survival (Hazard ratio=2.450, P=0.032). HOXA11-AS overexpression enhanced cell proliferation, migration, and tumor invasion in vitro, whereas HOXA11-AS knockdown inhibited these biologic aggressive features. These adverse changes were accompanied by characteristics of epithelial-mesenchymal transition (EMT). In vivo xenograft experiments using the siHOXA11-AS-transfected HeLa cells revealed that HOXA11-AS strongly induced tumor growth. Furthermore, we found that HOXA11-AS knockdown decreased cancer stemness and triggered the EMT program. In conclusion, HOXA11-AS overexpression correlated with poor survival in patients with cervical cancer. Thus, HOXA11-AS may be a pivotal target for exploring novel cervical cancer therapeutics.
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