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

// Maria Lee 1, 2, * , Hee Jung Kim 3, * , Sang Wun Kim 3 , Sun-Ae Park 3 , Kyung-Hee Chun 4 , Nam Hoon Cho 5 , Yong Sang Song 1 , Young Tae Kim 3 1 Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea 2 Department of Obstetrics and Gynecology, Yonsei University Graduate School, Seoul, Korea 3 Institute of Women’s Life Medical Science, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea 4 Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea 5 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Young Tae Kim, email: ytkchoi@yuhs.ac Keywords: HOTAIR, long non-coding RNA, invasion, prognosis, cervical cancer Received: February 25, 2016      Accepted: May 29, 2016      Published: June 15, 2016 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.