Mir-200c inhibits HOTAIR expression resulting in the decrease of chemoresistance in ovarian cancer stem cells
Mir-200c inhibits HOTAIR expression resulting in the decrease of chemoresistance in ovarian cancer stem cells
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Mir-200c 抑制 HOTAIR 表达，导致卵巢癌干细胞化疗耐药性降低
DOI：
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发表时间：
2016
影响因子：
0.1
通讯作者：
Dou Jun
中科院分区：
文献类型：
--
作者：
Wang Jing;Chen Dengyu;Shi Fangfang;Chen Junsong;Zhang Yuxia;Shi Fangfang;Wu Di;Li Miao;Pan Meng;Dou Jun
在本研究中，我们研究了miR-200C过表达是否会通过下调LncRNA HOTAIR来增加上皮性卵巢癌干细胞(EOC)对化疗药物的敏感性。我们使用磁激活细胞分选系统从稳定转导慢病毒miR-200C的人卵巢癌SKOV3细胞中分离出SKOV3 CD44(+)CD117(+)干细胞。用野生型和突变区的HOTAIR荧光素酶对miR-200C的直接靶标HOTAIR进行了验证。结果表明，与慢病毒模型转导的SKOV3 CD44(+)CD117(+)CSCs或野生型SKOV3 CD44(+)CD117(+)CSCs相比，在SKOV3 CD44(+)CD117(+)CSCs中过表达miR-200C可显著降低对紫杉醇和顺铂的耐药性。此外，与不表达miR-200C的SKOV3 CD44(+)CD117(+)CSCs相比，高表达miR-200C的SKOV3 CD44(+)CD117(+)CSCs显著降低了其从肿瘤组织到裸鼠肺的转移潜能。HOTAIR的直接下调依赖于miR-200C，因为荧光素酶报告和补救实验结果表明，假定的miR-200C结合位点对HOTAIR的表达具有抑制作用。总之，SKOV3 CD44(+)CD117(+)CSCs对紫杉醇或顺铂的敏感性增加可能是通过miR-200C的过度表达来调节的，miR-200C直接抑制HOTAIR的表达。
In this study, we investigated whether miR-200c overexpression would increase the sensitivity of epithelial ovarian cancer (EOC) stem cells (CSCs) to chemotherapy drugs through down-regulation of lncRNA HOTAIR. We used a magnetic-activated cell sorting system to isolate the SKOV3 CD44(+)CD117(+)CSCs from the selected human EOC SKOV3 cells that were stably transduced with lentivirus miR-200c. HOTAIR, a direct target of miR-200c, was validated by using the wild-type and the mutant region HOTAIR luciferase reporters. The results showed the overexpression of miR-200c in SKOV3 CD44(+)CD117(+)CSCs significantly decreased the drug resistant to paclitaxel and cisplatin compared with SKOV3 CD44(+) CD117(+) CSCs transduced with the lentivirus-mock or the wild-type of SKOV3 CD44(+) CD117(+)CSCs. Moreover, SKOV3 CD44(+) CD117(+)CSCs with miR-200c overexpression dramatically reduced its metastatic potential from the tumor tissues to the nude mouse lungs in contrast to SKOV3 CD44(+)CD117(+)CSCs without miR-200c overexpression. The direct down-regulation of HOTAIR was miR-200c dependent because luciferase reporter and rescue assay results showed that the putative miR-200c-binding site has the inhibitory effect on HOTAIR expression. Collectively, the increased sensitivity of SKOV3 CD44(+)CD117(+)CSCs to paclitaxel or cisplatin may be modulated by overexpression of miR-200c that directly inhibits HOTAIR expression.
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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：
5.8
作者：
Wang J;Chen D;He X;Zhang Y;Shi F;Wu D;Chen J;Zhang Y;Zhao F;Dou J
通讯作者：
Dou J
影响因子：
1.6
作者：
Dou, J.;Li, Y.;Gu, N.
通讯作者：
Gu, N.
影响因子：
3.8
作者：
Prislei S;Martinelli E;Mariani M;Raspaglio G;Sieber S;Ferrandina G;Shahabi S;Scambia G;Ferlini C
通讯作者：
Ferlini C
MiR-200 家族的表观遗传激活有助于 H19 介导的肝细胞癌转移抑制。
影响因子：
4.7
作者：
Zhang, Ling;Yang, Fu;Sun, Shu-han
通讯作者：
Sun, Shu-han