The development of long non-coding RNA HOTAIR as a serum biomarker in cervical cancer by notch targeting pathway
Other Titles
자궁경부암에서 혈청 바이오마커로 Notch 신호경로를 통한 긴 비 암호화 RNA인 HOTAIR의 개발
Authors
이마리아
Issue Date
2016
Description
Dept. of Medicine/박사
Abstract
HOTAIR is a long non-coding RNAs (lncRNA) that plays a role as an oncogenic molecule in cervical cancer. In this study, we investigated in detail the expression of serum HOTAIR, as well as its functions, in cervical cancer. Serum HOTAIR expression was assessed by qRT-PCR and the results were compared with clinicopathologic factors, including survival data. The effects of HOTAIR overexpression via lentiviral transfection were examined in SiHa cells and a xenograft model. The expression of HOTAIR in cervical cancer serum was significantly higher than in the control groups (P < 0.001), and this increase of expression was significantly associated with tumor size (P = 0.030), lymphovascular space invasion (P = 0.037), and lymph node metastasis (P = 0.043). In univariate analysis, disease free survival and overall survival in cervical cancer was significantly shorter in cases with high HOTAIR expression (hazard ratio [HR] = 4.27, 4.68 and P = 0.039, 0.031, respectively). HOTAIR overexpression in cervical cancer cells resulted in increase of cell proliferation and invasion in vitro, whereas HOTAIR knockdown inhibited these properties and increased apoptosis. In addition, in vivo experiments using HOTAIR overexpression clearly showed a strong inducer of tumor growth and a modulation of expression of epithelial-mesenchymal transition and Notch signaling pathway related genes, further suggesting that HOTAIR overexpression can promote cell proliferation and invasion. Taken together, increased serum HOTAIR expression is associated with poor survival outcome in cervical cancer, and HOTAIR may represent a useful therapeutic target in cervical cancer patients.