The long non-coding RNA HOTAIR increases tumour growth and invasion in cervical cancer

Evidence suggests that the long non-coding RNA (lncRNA), HOTAIR, is involved in cervical cancer pathogenesis. Researchers at the Seoul National University College of Medicine examined serum HOTAIR expression levels in cervical cancer patients and determined the relationships between HOTAIR expression and several clinic pathological factors, including survival. They 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 tumor 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 tumor 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.

Effect of HOTAIR on tumour growth in vivo

A. SiHa cells (5×106) stably expressing HOTAIR were inoculated into nude mice, and the effect of HOTAIR on cervical tumour growth was examined after 50 days (n = 6). A photograph of the tumours is presented. B. Tumour volume was calculated every 3 days. Data are mean ± SD (n = 6). *P < 0.05 and ** P < 0.001 vs. control. C. Tumour weight. Data are mean ± SD. D. qRT-PCR analysis of HOTAIR expression in tissues of resected tumours. E. Haematoxylin and eosin staining at 50 days after injection. F. MRI imaging. G. Micro PET image with transverse (a), coronal (b), and sagittal (c) plane slices of mice showing FDG uptake in the affected right carotid artery (arrows).