E2F1-induced upregulation of long noncoding RNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs.
E2F1-induced upregulation of long noncoding RNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs.
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E2F1 诱导的长链非编码 RNA LINC00668 的上调可预测胃癌的不良预后，并通过 CKI 的表观遗传沉默促进细胞增殖。
DOI：
10.18632/oncotarget.6745
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发表时间：
2016-04-26
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Zhang E;Yin D;Han L;He X;Si X;Chen W;Xia R;Xu T;Gu D;De W;Guo R;Xu Z;Chen J
最近，长非编码RNA(LncRNAs)被证明在人类癌症生物学中具有重要的调节作用。通过利用公开可用的LncRNAs表达谱数据并结合分析，我们筛选出LINC00668，其表达显著增加，并与胃癌(GC)的预后相关。进一步的实验表明，LINC00668基因敲除显著抑制了体外和体内的增殖。机制研究表明，LINC00668是E2F转录因子1(E2F1)的直接转录靶点。我们进一步证明了LINC00668与PRC2相关，并且这种关联是表观遗传抑制细胞周期蛋白依赖性蛋白激酶抑制物(CKI)所必需的，包括p15、p16、p21、p27和p57，从而有助于调节胃癌细胞周期。我们的结果表明，E2F1激活的LINC00668作为细胞周期调节因子，丰富了lncRNA和E2F1介导的细胞周期调控途径之间的机制联系，可能成为预测胃癌预后的候选生物标志物和新的治疗靶点。
Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. By utilizing publicly available lncRNAs expression profiling data and integrating analyses, we screened out LINC00668, whose expression is significantly increased and correlated with outcomes in gastric cancer (GC). Further experiments revealed that LINC00668 knockdown significantly repressed proliferation, both in vitro and in vivo. Mechanistic investigations showed that LINC00668 was a direct transcriptional target of E2F transcription factor 1 (E2F1). We further demonstrated that LINC00668 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15, p16, p21, p27 and p57, thus contributing to the regulation of the gastric cancer cell cycle. Our results suggest that E2F1-activated LINC00668, as a cell cycle regulator, enriches the mechanistic link between lncRNA and the E2F1-mediated cell cycle regulation pathway and may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.
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影响因子：
8
作者：
Braconi, C.;Kogure, T.;Valeri, N.;Huang, N.;Nuovo, G.;Costinean, S.;Negrini, M.;Miotto, E.;Croce, C. M.;Patel, T.
通讯作者：
Patel, T.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.1
作者：
Gu, Wei;Gao, Tian;Hu, Meijie
通讯作者：
Hu, Meijie
影响因子：
50.3
作者：
Hu X;Feng Y;Zhang D;Zhao SD;Hu Z;Greshock J;Zhang Y;Yang L;Zhong X;Wang LP;Jean S;Li C;Huang Q;Katsaros D;Montone KT;Tanyi JL;Lu Y;Boyd J;Nathanson KL;Li H;Mills GB;Zhang L
通讯作者：
Zhang L
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y