miR-375 mediated acquired chemo-resistance in cervical cancer by facilitating EMT.
miR-375 mediated acquired chemo-resistance in cervical cancer by facilitating EMT.
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miR-375 通过促进 EMT 介导宫颈癌获得性化疗耐药
DOI：
10.1371/journal.pone.0109299
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Shen Y;Zhou J;Li Y;Ye F;Wan X;Lu W;Xie X;Cheng X
获得性耐药是癌症死亡的主要原因之一。越来越多的证据表明，miRNA和上皮-间质转化在癌症的化疗耐药性中起着关键作用。在这里，我们显示了宫颈癌中紫杉醇耐药与miR-375过表达和上皮-间质转化诱导的相关性。使用不同的宫颈癌细胞模型，我们发现紫杉醇瞬时诱导miR-375表达上调，增殖抑制，从上皮细胞向间质细胞表型转化，从而损害紫杉醇敏感性。miR-375的强制过表达可能通过直接靶向途径抑制Ecadherin的表达，从而导致紫杉醇耐药。结果表明，Ecadherin的再表达部分逆转了上皮-间充质转化表型和miR-375诱导的紫杉醇耐药。我们的研究结果表明紫杉醇诱导的miR-375过表达通过直接靶向Ecadherin促进上皮-间质转化过程，抑制增殖，从而导致宫颈癌细胞的化疗耐药性。逆转miR-375或Ecadherin的表达可能是克服宫颈癌化疗耐药性的一种新的治疗方法。
Acquired chemo-resistance is one of the key causal factors in cancer death. Emerging evidences suggest that miRNA and epithelial–mesenchymal transition play critical roles in the chemo-resistance in cancers. Here, we showed the association of paclitaxel-resistance with miR-375 over-expression and epithelial–mesenchymal transition inducement in cervical cancer. Using different cervical cancer cell models, we found that paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial–mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial–mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells. A reversion of miR-375 or Ecadherin expression may be a novel therapeutic approach for overcoming chemo-resistance in cervical cancer.
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影响因子：
11.5
作者：
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通讯作者：
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影响因子：
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影响因子：
3.7
作者：
Li, Yiwei;Kong, Dejuan;Wang, Zhiwei;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.