Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition.
Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition.
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DOI：
10.1186/s12935-015-0174-4
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发表时间：
2015
影响因子：
5.8
通讯作者：
Dou J
中科院分区：
文献类型：
--
作者：
Wang J;Chen D;He X;Zhang Y;Shi F;Wu D;Chen J;Zhang Y;Zhao F;Dou J
新出现的证据表明，失调的长间插非编码RNA（lincRNA）HOTAIR与肿瘤侵袭和转移高度相关，但HOTAIR的高表达与癌症干细胞（CSC）的转移级联之间的联系需要进一步研究。本研究旨在探讨HOTAIR表达下调对上皮性卵巢癌（EOC）CSCs肿瘤发生和转移的影响。采用磁激活细胞分选系统从人卵巢癌SKOV 3细胞系中分离CD 117 + CD 44 +CSCs，并将基于表达载体的HOTAIR靶向小发夹RNA转染，选择稳定转染的细胞进行研究。进行集落形成、伤口愈合、细胞转移和致瘤性测定。结果表明，HOTAIR在卵巢癌组织和卵巢癌3型CD 117 + CD 44+肿瘤干细胞中的表达高于卵巢癌3型肿瘤组织和非CD 117 + CD 44+肿瘤干细胞。与CD 117 + CD 44 +- scramble相比，CD 117 + CD 44 +-shHOTAIR显示抑制HOTAIR表达，降低细胞迁移和侵袭，表明抑制上皮-间充质转化。HOTAIR在CD 117 + CD 44 + CSCs中的表达下调可显著抑制肿瘤的生长和肺转移。我们的研究结果表明，在CD 117 + CD 44 + CSC中，shHOTAIR介导的HOTAIR表达下调可能是未来临床试验的一个有希望的新机会。
Emerging evidence indicates that dysregulated long intervening non-coding RNA (lincRNA) HOTAIR correlates highly with tumor invasion and metastasis but a link between the high expression of HOTAIR and the metastatic cascade of cancer stem cells (CSCs) needs to be further studied. The purpose of this study was to investigate the effect of down-regulated HOTAIR expression on tumorgeniesis and metastasis of epithelial ovarian cancer (EOC) CSCs. CD117+CD44+CSCs were isolated from human EOC SKOV3 cell line by using a magnetic-activated cell sorting system, and were then transfected with the expression vector-based small hairpin RNA targeting HOTAIR; the stably transfected cells were selected for the study. Colony-forming, wound-healing, cellular metastasis and tumorigenicity assays were performed. The results demonstrated that the HOTAIR expression in clinical EOC tissues and SKOV3 CD117+CD44+CSCs was higher than in SKOV3 tumor tissues and non-CD117+CD44+CSCs. The CD117+CD44+-shHOTAIR showed an inhibited HOTAIR expression, reduced cell migration and invasion than CD117+CD44+- scramble, suggesting the inhibition of an epithelial-mesenchymal transition. Moreover, the downregulated HOTAIR expression in CD117+CD44+ CSCs significantly decreased the tumor growth and lung metastasis in xenograft mice. Our findings demonstrated the shHOTAIR-mediated down-regulation of the HOTAIR expression in CD117+CD44+ CSCs can be a promising new opportunity for future clinical trials.
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影响因子：
4
作者：
Chen D;Zhang Y;Wang J;Chen J;Yang C;Cai K;Wang X;Shi F;Dou J
通讯作者：
Dou J
影响因子：
8.8
作者：
Shen, B.;Chu, E. S. H.;Zhao, G.;Man, K.;Wu, C-W;Cheng, J. T. Y.;Li, G.;Nie, Y.;Lo, C. M.;Teoh, N.;Farrell, G. C.;Sung, J. J. Y.;Yu, J.
通讯作者：
Yu, J.
影响因子：
64.8
作者：
通讯作者：
--
长链非编码RNA HOTAIR的过度表达可预测上皮性卵巢癌患者的不良预后并促进肿瘤转移
影响因子：
4.7
作者：
Qiu, Jun-jun;Lin, Ying-ying;Hua, Ke-qin
通讯作者：
Hua, Ke-qin
影响因子：
64.5
作者：
Rinn, John L.;Kertesz, Michael;Chang, Howard Y.
通讯作者：
Chang, Howard Y.