TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling.
TGF-β-induced NKILA inhibits ESCC cell migration and invasion through NF-κB/MMP14 signaling.
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TGF-β诱导的NKILA通过NF-κB/MMP14信号抑制ESCC细胞迁移和侵袭
DOI：
10.1007/s00109-018-1621-1
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Lu Z;Chen Z;Li Y;Wang J;Zhang Z;Che Y;Huang J;Sun S;Mao S;Lei Y;Gao Y;He J
转化生长因子β（TGF-β）信号通路在绝大多数癌症中起抗肿瘤和促肿瘤作用，并且已报道长非编码RNA在高度相关的反应过程中起关键作用。然而，长链非编码RNA（lncRNA）在食管鳞状细胞癌（ESCC）中TGF-β信号转导中的作用尚不清楚。在这项研究中，我们通过RNA-seq比较TGF-β1处理和未处理的ESCC细胞之间的lncRNA表达水平，并观察到经典TGF-β信号通路显著上调NF-κ B相互作用lncRNA（NKILA）。使用RT-qPCR对39对ESCC肿瘤和相邻非肿瘤样品的RNA分析表明，NKILA在ESCC肿瘤组织中显著下调，并且与早期阶段（I和II）相比，晚期肿瘤组织（III和IV）中NKILA表达水平显著降低（p < 0.01）。功能获得和功能丧失实验表明NKILA抑制ESCC细胞的体内外转移，其机制研究表明NKILA通过抑制IκBα磷酸化和NF-κB活化抑制MMP 14的表达。总的来说，这些发现表明TGF-β诱导的lncRNA NKILA具有作为抗转移疗法的潜力。长链非编码RNA NKILA可通过经典的TGF-β信号通路在食管鳞癌中显著上调。NKILA在食管鳞状细胞癌中表达明显下调，且与TNM分期呈负相关。NKILA通过抑制IκBα的磷酸化和NF-κB的活化，抑制MMP 14的表达，从而抑制食管鳞癌细胞的转移。本文的在线版本（10.1007/s 00109 -018-1621-1）包含补充材料，可供授权用户使用。
The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β signaling in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we performed RNA-seq to compare lncRNAs expression levels between TGF-β1-treated and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA) was remarkably upregulated by the classical TGF-β signaling pathway. RNA profiling of 39 pairs ESCC tumor and adjacent nontumor samples using RT-qPCR demonstrated that NKILA is significantly downregulated in ESCC tumor tissues, and NKILA expression levels were significantly decreased in advanced tumor tissues (III and IV) compared to early stages (I and II) (p < 0.01). Gain- and loss-of-function assays showed that NKILA inhibited ESCC cell metastasis in vitro and in vivo, and mechanism studies showed that NKILA repressed MMP14 expression by inhibiting IκBα phosphorylation and NF-κB activation. Collectively, these findings suggest that the TGF-β-induced lncRNA NKILA has potential as an antimetastasis therapy. Long noncoding RNA NKILA could be remarkably upregulated by classical TGF-β signal pathway in ESCC. NKILA was significantly downregulated in esophageal squamous cell carcinoma and negatively correlated with TNM stage. NKILA inhibits ESCC cell metastasis via repressing MMP14 expression by suppressing the phosphorylation of IκBα and NF-κB activation. The online version of this article (10.1007/s00109-018-1621-1) contains supplementary material, which is available to authorized users.
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影响因子：
8.8
作者：
Akanuma, N.;Hoshino, I.;Akutsu, Y.;Murakami, K.;Isozaki, Y.;Maruyama, T.;Yusup, G.;Qin, W.;Toyozumi, T.;Takahashi, M.;Suito, H.;Hu, X.;Sekino, N.;Matsubara, H.
通讯作者：
Matsubara, H.
影响因子：
24.5
作者：
Li J;Chen Z;Tian L;Zhou C;He MY;Gao Y;Wang S;Zhou F;Shi S;Feng X;Sun N;Liu Z;Skogerboe G;Dong J;Yao R;Zhao Y;Sun J;Zhang B;Yu Y;Shi X;Luo M;Shao K;Li N;Qiu B;Tan F;Chen R;He J
通讯作者：
He J
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
DOI：
10.1186/s13046-017-0518-0
发表时间：
2017-04-17
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Lu Z;Li Y;Wang J;Che Y;Sun S;Huang J;Chen Z;He J
通讯作者：
He J
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D