HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer.
HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer.
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DOI：
10.1038/onc.2012.193
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发表时间：
2013-03-28
期刊：
影响因子：
8
通讯作者：
Safe, S.
中科院分区：
文献类型：
--
作者：
Kim, K.;Jutooru, I.;Chadalapaka, G.;Johnson, G.;Frank, J.;Burghardt, R.;Kim, S.;Safe, S.
HOTAIR是一种与多梳抑制复合物2（PRC2）相关的长插入非编码RNA（lincRNA），并且过表达与乳腺癌、结肠癌和肝癌患者的不良存活相关。在这项研究中，我们发现HOTAIR在胰腺肿瘤中的表达高于非肿瘤组织，并且与更具侵袭性的肿瘤相关。通过RNA干扰敲低HOTAIR（siHOTAIR）显示HOTAIR在胰腺癌细胞侵袭中起重要作用，并且如在其他癌细胞系中所报道的。相比之下，在过表达该lincRNA的Pancl和L3.6pL胰腺癌细胞中HOTAIR敲低降低了细胞增殖，改变了细胞周期进程，并诱导了细胞凋亡，表明与其他癌细胞系相比，HOTAIR在胰腺癌细胞中的功能扩展。基因阵列研究的结果表明，在胰腺癌细胞与乳腺癌细胞中HOTAIR调节的基因之间存在最小的重叠，并且HOTAIR独特地抑制了胰腺癌细胞和肿瘤中与细胞周期进展相关的几个干扰素相关基因和基因集。在Panc1和L3.6 pL细胞中HOTAIR抑制的选定基因的分析表明，通过敲低EZH2和染色质免疫沉淀分析，HOTAIR介导的基因抑制是PRC2依赖性和非依赖性的。HOTAIR在L3.6pL细胞中的敲低抑制了小鼠异种移植模型中的肿瘤生长，进一步证明了HOTAIR在胰腺癌中的促癌功能。
HOTAIR is a long intervening non-coding RNA (lincRNA) that associates with the Polycomb Repressive Complex 2 (PRC2) and overexpression is correlated with poor survival for breast, colon and liver cancer patients. In this study, we show that HOTAIR expression is increased in pancreatic tumors compared to non-tumor tissue and is associated with more aggressive tumors. Knockdown of HOTAIR (siHOTAIR) by RNA interference shows that HOTAIR plays an important role in pancreatic cancer cell invasion and as reported in other cancer cell lines. In contrast, HOTAIR knockdown in Panc1 and L3.6pL pancreatic cancer cells that overexpress this lincRNA decreased cell proliferation, altered cell cycle progression, and induced apoptosis, demonstrating an expanded function for HOTAIR in pancreatic cancer cells compared to other cancer cell lines. Results of gene array studies showed that there was minimal overlap between HOTAIR-regulated genes in pancreatic vs. breast cancer cells and HOTAIR uniquely suppressed several interferon-related genes and gene sets related to cell cycle progression in pancreatic cancer cells and tumors. Analysis of selected genes suppressed by HOTAIR in Panc1 and L3.6 pL cells showed by knockdown of EZH2 and chromatin immunoprecipitation assays that HOTAIR-mediated gene repression was both PRC2-dependent and -independent. HOTAIR knockdown in L3.6pL cells inhibited tumor growth in mouse xenograft model, further demonstrating the pro-oncogenic function of HOTAIR in pancreatic cancer.
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影响因子：
64.8
作者：
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作者：
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通讯作者：
Safe, S.
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