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

// Hee Jung Kim 1, * , Kyung Jin Eoh 1, 2, * , Lee Kyung Kim 1 , Eun Ji Nam 1 , Sun Och Yoon 3 , Kun-Hong Kim 4 , Jae Kwan Lee 5 , Sang Wun Kim 1 , Young Tae Kim 1 1 Institute of Women's Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea 2 Department of Obstetrics and Gynecology, Yonsei University Graduate School, Seoul, Korea 3 Department of Pathology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul, Korea 4 Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea 5 Department of Obstetrics and Gynecology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Sang Wun Kim, email: san1@yuhs.ac Young Tae Kim, email: ytkchoi@yuhs.ac Keywords: HOXA11 antisense, long noncoding RNA, invasion, prognosis, cervical cancer Received: August 08, 2016     Accepted: October 14, 2016     Published: October 25, 2016 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.