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Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2)

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Tumor Biology

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression through the endogenous RNA interference machinery. Treatments with combination of chemotherapy with surgery are essential for advanced-stage colorectal cancer. However, the development of chemoresistance is a major obstacle for clinical application of anticancer drugs. In this study, we report a miR-203-SIK2 axis that involves in the regulation of Taxol sensitivity in colon cancer cells. MiR-203 is downregulated in human colon tumor specimens and cell lines compared with their normal counterparts. We report miR-203 is correlated with Taxol sensitivity: overexpression of miR-203 sensitizes colon cancer cells and the Taxol-resistant cells display downregulated miR-203 compared with Taxol-sensitive cells. We identify SIK2 as a direct target of miR-203 in colorectal cancer cells. Overexpression of miR-203 complementary pairs to the 3′ untranslated region (UTR) of SIK2, leading to the sensitization of Taxol resistant cells. In addition, miR-203 and the salt-inducible kinase 2 (SIK2) are reverse expressed in human colorectal tumors. Finally, we demonstrate recovery of SIK2 by overexpression of SIK2-desensitized Taxol-resistant cells, supporting the miR-203-mediated sensitization to Taxol, is through the inhibition of SIK2. In general, our study will provide mechanisms of the microRNA-based anti-tumor therapy to develop anti-chemoresistance drugs.

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Acknowledgments

The authors would like to acknowledge all the staff and faculty working in China-Japan Union Hospital of Jilin University. We thank Dr. Xuebo Chen for providing the colorectal tumor patient samples at Department of General Surgery, China-Japan Union Hospital of Jilin University. This project is supported by the Dr. Bethune youth scientific research funds from Jilin University.

Author contributions

Y.L., S.G., and X.F. designed research; Y.L., S.G., X.C., M.L., and C.M. performed research; Y.L., S.G., X.C., M.L., C.M., and X.F. analyzed data; and Y.L., S.G., X.C., and X.F. wrote the paper.

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Authors and Affiliations

  1. Department of Anesthesia, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, China

    Yingyi Liu & Sujie Gao

  2. Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, China

    Xuebo Chen & Xuedong Fang

  3. Department of Ultrasonography, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, China

    Meihan Liu

  4. Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, China

    Cuiying Mao

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  1. Yingyi Liu
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  2. Sujie Gao
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  3. Xuebo Chen
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  4. Meihan Liu
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  6. Xuedong Fang
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Corresponding author

Correspondence to Xuedong Fang.

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This study was approved by the Medical Ethics Committee of the Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China, and written informed consent was obtained from the patients or their parents prior to sample collection.

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Liu, Y., Gao, S., Chen, X. et al. Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2). Tumor Biol. 37, 12231–12239 (2016). https://doi.org/10.1007/s13277-016-5066-2

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  • DOI: https://doi.org/10.1007/s13277-016-5066-2

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