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长链非编码 RNA HOTAIR 的上调促进食管鳞状细胞癌转移和不良预后。

Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.

机构信息

Department of Surgical Oncology, Affiliated Nanjing Hospital of Nanjing Medical University and Oncology Center of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Mol Carcinog. 2013 Nov;52(11):908-15. doi: 10.1002/mc.21944. Epub 2012 Jul 31.

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.

摘要

最近的研究表明,长链非编码 RNA(lncRNA)在癌症的发生和发展中的个体功能,HOX 转录反义 RNA(HOTAIR)能够重新编程染色质组织并促进癌细胞转移。为了确定 lncRNA HOTAIR 的表达模式,并评估其在食管鳞状细胞癌(ESCC)发生和发展中的生物学作用,从 78 名患者中收集 ESCC 组织和相邻非癌组织中的 HOTAIR 表达,并通过实时逆转录聚合酶链反应(RT-PCR)进行测量。还分析了 HOTAIR 与临床病理特征和预后的相关性。通过 siRNA 处理抑制 HOTAIR 的表达,以探讨其在肿瘤进展中的作用。与相邻的非癌组织相比,癌组织中 HOTAIR 的表达水平显著升高(96%,P<0.01),与癌症转移(P<0.01)、升高的 TNM(2009)分期分类(P<0.01)和降低的总生存率(P=0.003)高度相关。多变量分析显示,HOTAIR 表达(P=0.003)也是比较 TNM 分期(P=0.024)和淋巴结转移(P=0.010)的独立预后因素。此外,对 ESCC 细胞系 KYSE30 的体外检测表明,下调 HOTAIR 降低了细胞侵袭和迁移能力,同时增加了细胞对凋亡的反应。因此,HOTAIR 是一种参与 ESCC 进展和预后的新型分子。充分阐明与 ESCC 相关的 HOTAIR 功能可能为 lncRNA 在识别 ESCC 和其他常见癌症的新型药物靶点和治疗方法方面开辟途径。

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