A novel lncRNA, LUADT1, promotes lung adenocarcinoma proliferation via the epigenetic suppression of p27.
A novel lncRNA, LUADT1, promotes lung adenocarcinoma proliferation via the epigenetic suppression of p27.
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一种新型 lncRNA LUADT1 通过 p27 的表观遗传抑制促进肺腺癌增殖。
DOI：
10.1038/cddis.2015.203
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发表时间：
2015-08-20
影响因子：
9
通讯作者：
Xu L
中科院分区：
文献类型：
--
作者：
Qiu M;Xu Y;Wang J;Zhang E;Sun M;Zheng Y;Li M;Xia W;Feng D;Yin R;Xu L
已知长链非编码RNA（lncRNA）调节各种癌症的发展和进展。然而，在肺腺癌（LUAD）中很少有lncRNA被充分表征。在这里，我们确定了lncRNA和蛋白质编码基因的表达谱，通过微阵列分析配对LUAD组织和相邻的非肿瘤组织从五个女性非吸烟者与LUAD。LUAD组织和配对的正常组织之间共有498个lncRNA和1691个蛋白质编码基因差异表达。LUAD转录本1（LUADT 1）是一种新的lncRNA，在LUAD中高度表达，与T分期相关。体外和体内实验结果均表明，LUADT 1基因敲低可显著抑制LUAD细胞的增殖，并诱导细胞周期阻滞于G 0-G1期。进一步的分析表明LUADT 1可能通过表观遗传学抑制p27的表达来调节细胞周期进程。RNA免疫沉淀和染色质免疫沉淀试验证实，LUADT 1结合到SUZ 12，一个核心组成部分的polycomb抑制复合物2，并介导的三甲基化H3 K27在p27的启动子区域。LUADT 1和p27表达之间的负相关性在LUAD组织样本中得到证实。这些数据表明，一组lncRNA和蛋白质编码基因在LUAD中差异表达。LUADT 1是一种调节LUAD进展的致癌lncRNA，这表明失调的lncRNA可能是LUAD进展的关键调节因子。
Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of various cancers. However, few lncRNAs have been well characterized in lung adenocarcinoma (LUAD). Here, we identified the expression profile of lncRNAs and protein-coding genes via microarrays analysis of paired LUAD tissues and adjacent non-tumor tissues from five female non-smokes with LUAD. A total of 498 lncRNAs and 1691 protein-coding genes were differentially expressed between LUAD tissues and paired adjacent normal tissues. A novel lncRNA, LUAD transcript 1 (LUADT1), which is highly expressed in LUAD and correlates with T stage, was characterized. Both in vitro and in vivo data showed that LUADT1 knockdown significantly inhibited proliferation of LUAD cells and induced cell cycle arrest at the G0–G1 phase. Further analysis indicated that LUADT1 may regulate cell cycle progression by epigenetically inhibiting the expression of p27. RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that LUADT1 binds to SUZ12, a core component of polycomb repressive complex 2, and mediates the trimethylation of H3K27 at the promoter region of p27. The negative correlation between LUADT1 and p27 expression was confirmed in LUAD tissue samples. These data suggested that a set of lncRNAs and protein-coding genes were differentially expressed in LUAD. LUADT1 is an oncogenic lncRNA that regulates LUAD progression, suggesting that dysregulated lncRNAs may serve as key regulatory factors in LUAD progression.