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MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK

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Tumor Biology

Abstract

Chemotherapy is the preferred therapeutic approach for the therapy of advanced ovarian cancer, but 5-year survival rate remains low due to the development of drug resistance. Increasing evidence has documented that microRNAs (miRNAs) act important roles in drug resistance in a variety types of cancer. However, the roles of miRNA in regulating Taxol resistance in ovarian cancer and the detailed mechanism are less reported. We used Taqman probe stem loop real-time PCR to accurately measure the levels of miR-197 in normal ovarian cells, ovarian cancer cells, and Taxol-resistant ovarian cancer cells and found that miR-197 was significantly increased in Taxol-resistant ovarian cancer cells. Enforced expression of miR-197 can promote Taxol resistance, cell proliferation, and invasion of ovarian cancer cells. Meanwhile, repression of miR-197 in ovarian cancer cells can sensitize its response to Taxol and also induced attenuated cell proliferation and invasion ability. Furthermore, investigation of the detailed mechanism showed that the promotion of miR-197 on drug resistance in ovarian cancer cells was partially mediated by downregulating NLK, a negative regulator of WNT signaling pathway. Taken together, our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells.

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Acknowledgments

This work was supported by the Health Bureau of Chongqing (2013-2-121).

Conflicts of interest

None

Authors’ contributions

Q. Z. conceived the project; D.-L. Z. and L. Y. designed the experiments and carried out the majority of the experiments; X.-T. L. and R. L. helped to collect clinical samples; all authors discussed the results; D. W. and D.-L. Z. wrote the manuscript.

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Authors and Affiliations

  1. Department of Gynecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China

    Dongling Zou, Dong Wang, Rong Li, Ying Tang, Li Yuan, Xingtao Long & Qi Zhou

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  1. Dongling Zou
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  2. Dong Wang
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  3. Rong Li
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  4. Ying Tang
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  7. Qi Zhou
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Correspondence to Qi Zhou.

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Zou, D., Wang, D., Li, R. et al. MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK. Tumor Biol. 36, 6725–6732 (2015). https://doi.org/10.1007/s13277-015-3365-7

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  • DOI: https://doi.org/10.1007/s13277-015-3365-7

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