A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit.
A novel long non-coding RNA lnc-GNAT1-1 is low expressed in colorectal cancer and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit.
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一种新型长非编码RNA lnc-GNAT1-1在结直肠癌中低表达，并通过调节RKIP-NF-kappaB-Snail回路发挥肿瘤抑制因子的作用。
DOI：
10.1186/s13046-016-0467-z
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发表时间：
2016-12-03
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Ye C;Shen Z;Wang B;Li Y;Li T;Yang Y;Jiang K;Ye Y;Wang S
背景长链非编码RNA（lncRNA）在结直肠癌（CRC）进展中的作用尚未完全阐明。本研究旨在报道一种新型lncRNA lnc-GNAT1-1的鉴定及其在CRC进展中的功能作用。方法在三对CRC原发组织和肝转移组织中进行lncRNA表达谱微阵列分析，并鉴定一种新型lncRNA lnc-GNAT1-1是一种潜在的功能性lncRNA。采用实时定量PCR检测其在结直肠癌组织、细胞系和患者血浆中的表达，采用细胞分级分离评估其亚细胞定位。通过siRNA敲除lnc-GNAT1-1或通过慢病毒载体过表达lnc-GNAT1-1，然后进行体外体内实验以评估其在CRC中的生物学作用和潜在机制。结果lnc-GNAT1-1在肝转移瘤中的表达较原发灶降低，而后者低于配对的正常粘膜。 lnc-GNAT1-1表达降低与CRC患者不利的临床病理特征和不良预后相关。在多变量分析中，lnc-GNAT1-1被证明是一个独立的预后因素。血浆中，CRC患者中lnc-GNAT1-1较健康供者显着降低，且随着TNM分期的进展，血浆lnc-GNAT1-1水平降低；受试者工作特征曲线（ROC曲线）显示血浆lnc-GNAT1-1对CRC具有中等至良好的诊断效率。体外实验表明，敲低lnc-GNAT1-1可以抑制CRC细胞系的侵袭性表型。体内研究表明，lnc-GNAT1-1的过表达可以抑制CRC细胞的肝转移。最后，我们探讨了lnc-GNAT1-1在CRC中发挥作用的潜在机制，发现lnc-GNAT1-1与Raf激酶抑制蛋白（RKIP）在细胞和患者组织中的表达呈正相关。我们进一步发现lnc-GNAT1-1可以调节CRC中的RKIP-NF-κB-Snail环路。结论我们在这项研究中证明了一种新的lncRNA，lnc-GNAT1-1，在结直肠癌组织和血浆中低表达，并通过调节RKIP-NF-κB-Snail环路发挥抑癌作用。
BackgroundThe role of long non-coding RNAs (lncRNAs) in colorectal cancer (CRC) progression has not fully been elucidated. This study was designed to report the identification of a novel lncRNA, lnc-GNAT1-1, and its functional role in CRC progression.MethodslncRNA expression profile microarray was performed in three paired primary and liver metastatic tissues of CRC, and a novel lncRNA, lnc-GNAT1-1, was identified to be a potential functional lncRNA. Quantitative real-time PCR was used to detect its expression in CRC tissues, cell lines, and patients’ plasma, cell fractionation was used to evaluate its subcellular location. lnc-GNAT1-1 was knockdown by siRNA or overexpressed by a lentivirus vector, then in vitro an vivo experiments were performed to evaluate its biological role and the underlying mechanisms in CRC.ResultsExpression of lnc-GNAT1-1 was decreased in liver metastasis than the primary tumor, while the later one is lower than the paired normal mucosa. Decreased lnc-GNAT1-1 expression was associated unfavorable clinicopathological features and a poor prognosis of CRC patients. In multivariate analysis, lnc-GNAT1-1 was proved to be an independent prognostic factor. In plasma, lnc-GNAT1-1 was significant decreased in CRC patients than healthy donors, and with the TNM stages advanced, the plasma lnc-GNAT1-1 level decreased; Receiver operating characteristic curve (ROC curve) showed that plasma lnc-GNAT1-1 had a moderate to well diagnostic efficiency for CRC. In vitro experiments showed that knockdown of lnc-GNAT1-1 could inhibit the aggressive phenotypes of CRC cell lines. In vivo study showed that overexpression of lnc-GNAT1-1 could suppress the liver metastasis of CRC cells. Finally, we explored the underlying mechanism of the role lnc-GNAT1-1 plays in CRC, and found a positive correlation between lnc-GNAT1-1 and Raf kinase inhibitor protein (RKIP) expression both in cells and in patients’ tissues. We further found that lnc-GNAT1-1 could regulate the RKIP-NF-κB-Snail circuit in CRC.ConclusionsWe have demonstrated in this study that a novel lncRNA, lnc-GNAT1-1, is low expressed in colorectal cancer tissues and plasma, and acts as a tumor suppressor through regulating RKIP-NF-κB-Snail circuit.
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影响因子：
2.3
作者：
Wang Hui-Jun;Chen Huo-Po;Liu Jiping
通讯作者：
Liu Jiping
RKIP抑制胃癌细胞的恶性表型
影响因子：
3
作者：
Zhang, X. M.;Gu, H.;Zhang, G. Y.
通讯作者：
Zhang, G. Y.
影响因子：
--
作者：
Lee TY;Liu CL;Chang YC;Nieh S;Lin YS;Jao SW;Chen SF;Liu TY
通讯作者：
Liu TY
影响因子：
--
作者：
Datar I;Qiu X;Ma HZ;Yeung M;Aras S;de la Serna I;Al-Mulla F;Thiery JP;Trumbly R;Fan X;Cui H;Yeung KC
通讯作者：
Yeung KC
影响因子：
2.4
作者：
Rapozzi, Valentina;Umezawa, Kazuo;Xodo, Luigi E.
通讯作者：
Xodo, Luigi E.