title: Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.
abstract: Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.
authors.affiliation: Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Fang-Jun
authors.initials: FJ
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.forename: Su-Qing
authors.initials: SQ
authors.lastname: Li
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Wu
authors.forename: Lv
authors.initials: L
authors.lastname: Ji
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Liu
authors.forename: Guo-Zhi
authors.initials: GZ
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Cao
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Xie
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Lv
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Cao
mesh_terms: D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding
keywords: HOTAIR; cancer prognosis; esophageal squamous cell carcinoma; lncRNA; metastasis