The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer.
The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer.
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长链非编码RNA HOTAIR提示非小细胞肺癌预后不良并促进转移
DOI：
10.1186/1471-2407-13-464
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发表时间：
2013-10-08
期刊：
影响因子：
3.8
通讯作者：
De W
中科院分区：
文献类型：
--
作者：
Liu XH;Liu ZL;Sun M;Liu J;Wang ZX;De W
背景识别与肿瘤相关的长链非编码RNA并研究其分子生物学功能对于理解肿瘤的分子生物学和进展具有重要意义。HOTAIR（HOX转录反义基因间RNA）与几种癌症有关;然而，其在非小细胞肺癌（NSCLC）中的作用尚不清楚。本研究的目的是研究HOTAIR在NSCLC中的表达模式，并评估其在肿瘤进展中的生物学作用和临床意义。方法采用定量逆转录聚合酶链反应（qRT-PCR）分析42例NSCLC组织和4株NSCLC细胞系中HOTAIR的表达。通过过表达和RNA干扰（RNAi）技术研究HOTAIR的生物学功能。通过MTT和集落形成实验评价HOTAIR对细胞增殖的影响，通过transwell实验评价细胞迁移和侵袭。尾静脉注射细胞用于研究裸鼠中的转移。通过蛋白质印迹分析测定HOTAIR靶标的蛋白质水平。组间差异进行了测试的显着性使用学生的t-检验（双尾）。ResultsHOTAIR是高度表达的NSCLC样品和细胞系相比，相应的正常同行。HOTAIR表达上调与NSCLC的病理分期、淋巴结转移有关。此外，HOTAIR高水平表达的患者预后相对较差。RNA干扰抑制HOTAIR可降低NSCLC细胞的体外迁移和侵袭能力，抑制体内转移。HOXA 5水平受到HOTAIR敲低或过表达的影响in vitro.ConclusionsOur研究结果表明，HOTAIR在NSCLC组织中显著上调，并部分通过下调HOXA 5调节NSCLC细胞的侵袭和转移。因此，HOTAIR可能代表一种新的不良预后标志物，是NSCLC干预的潜在治疗靶点。
BackgroundThe identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. HOTAIR (HOX transcript antisense intergenic RNA) has been implicated in several cancers; however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of HOTAIR in NSCLC and to evaluate its biological role and clinical significance in tumor progression.MethodsExpression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of HOTAIR. The effect of HOTAIR on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Tail vein injection of cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed).ResultsHOTAIR was highly expressed both in NSCLC samples and cell lines compared with corresponding normal counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi decreased the migration and invasion of NSCLC cellsin vitroand impeded cell metastasisin vivo. HOXA5 levels were affected by HOTAIR knockdown or over-expressionin vitro.ConclusionsOur findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
作者：
Raman, V;Martensen, SA;Sukumar, S
通讯作者：
Sukumar, S
影响因子：
56.9
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Bertone, P;Stolc, V;Snyder, M
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MicroRNA-196a通过靶向HOXA5促进非小细胞肺癌细胞增殖和侵袭
影响因子：
3.8
作者：
Liu XH;Lu KH;Wang KM;Sun M;Zhang EB;Yang JS;Yin DD;Liu ZL;Zhou J;Liu ZJ;De W;Wang ZX
通讯作者：
Wang ZX
影响因子：
7.3
作者：
Farazi, Thalia A.;Spitzer, Jessica I.;Morozov, Pavel;Tuschl, Thomas
通讯作者：
Tuschl, Thomas