Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer.
Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer.
复制标题
长非编码 RNA XIST 加速结直肠癌的转移并调节上皮间质转化
DOI：
10.1038/cddis.2017.421
复制
发表时间：
2017-08-24
影响因子：
9
通讯作者：
Xu RH
中科院分区：
文献类型：
--
作者：
Chen DL;Chen LZ;Lu YX;Zhang DS;Zeng ZL;Pan ZZ;Huang P;Wang FH;Li YH;Ju HQ;Xu RH
肿瘤进展和转移是结直肠癌（CRC）死亡的主要原因。长链非编码RNA（lncRNA）是包括人类癌症在内的多种疾病的重要调控因子。在这项研究中，我们发现lncRNA XIST在CRC细胞系和组织中过表达。lncRNA XIST的高表达与CRC患者的不良总生存率相关。lncRNA XIST的敲低在体外显著抑制CRC细胞增殖、侵袭、上皮-间质转化（EMT）和CRC干细胞形成以及在体内显著抑制肿瘤生长和转移。进一步的研究表明，lncRNA XIST的敲低显著增加了microRNA-200 b-3 p（miR-200 b-3 p）的表达，已经发现在CRC组织和细胞系中下调，并且荧光素酶活性测定表明lncRNA XIST可以与miR-200 b-3 p直接结合。此外，lncRNA XIST的敲低显著降低了miR-200 b-3 p的直接靶点ZEB 1的表达，并且由lncRNA XIST敲低引起的肿瘤抑制作用可以通过在CRC细胞中重新表达ZEB 1来挽救。总的来说，我们的研究证明了lncRNA XIST如何通过竞争miR-200 b-3 p来调节ZEB 1的表达来调节CRC的进展和转移。lncRNA XIST可用作预测CRC患者预后的生物标志物。
Tumor progression and metastasis is the main cause of death in colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer. In this study, we found that lncRNA XIST was overexpressed in CRC cell lines and tissues. High expression of lncRNA XIST was associated with adverse overall survival in CRC patients. Knockdown of lncRNA XIST remarkably inhibited CRC cell proliferation, invasion, epithelial–mesenchymal transition (EMT) and CRC stem cell formation in vitro as well as tumor growth and metastasis in vivo. Further study indicated that knockdown of lncRNA XIST markedly increased the expression of microRNA-200b-3p (miR-200b-3p) that has been found to be downregulated in CRC tissues and cell lines, and luciferase activity assay indicated that lncRNA XIST could bind directly with miR-200b-3p. Moreover, knockdown of lncRNA XIST significantly reduced the expression of ZEB1, which was the direct target of miR-200b-3p, and the tumor suppressive effects caused by knockdown of lncRNA XIST could be rescued by re-expression of ZEB1 in CRC cells. Overall, our study demonstrated how lncRNA XIST regulates CRC progression and metastasis by competing for miR-200b-3p to modulate the expression of ZEB1. lncRNA XIST may be used as a biomarker to predict prognosis in CRC patients.
登录
查看更多内容
H19/let-7/LIN28相互负调节电路促进乳腺癌干细胞维持
影响因子：
9
作者：
Peng F;Li TT;Wang KL;Xiao GQ;Wang JH;Zhao HD;Kang ZJ;Fan WJ;Zhu LL;Li M;Cui B;Zheng FM;Wang HJ;Lam EW;Wang B;Xu J;Liu Q
通讯作者：
Liu Q
影响因子：
4.7
作者：
Chen DL;Wang DS;Wu WJ;Zeng ZL;Luo HY;Qiu MZ;Ren C;Zhang DS;Wang ZQ;Wang FH;Li YH;Kang TB;Xu RH
通讯作者：
Xu RH
影响因子：
11.2
作者：
Khaitan, Divya;Dinger, Marcel E.;Perera, Ranjan J.
通讯作者：
Perera, Ranjan J.
影响因子：
4.7
作者：
Svoboda, Miroslav;Slyskova, Jana;Vodicka, Pavel
通讯作者：
Vodicka, Pavel
影响因子：
2.6
作者：
Weakley, Sarah M.;Wang, Hao;Yao, Qizhi;Chen, Changyi
通讯作者：
Chen, Changyi