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MiR-492 is functionally involved in Oxaliplatin resistance in colon cancer cells LS174T via its regulating the expression of CD147

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Abstract

Chemotherapy remains the core of anticancer treatment. However, despite the tremendous strides made in the development of targeted anticancer therapies, emergence of resistance to chemotherapeutic drugs is still a major obstacle in the successful management of resistant tumors. Therefore, profound investigation into the in-depth molecular mechanisms of drug resistance is essential and may hopefully translate into effective therapies that can flip the switch from drug resistance to susceptibility. To develop novel-targeted therapy holds promise for conquering chemotherapy resistance, one of the major hurdles in current colon cancer treatment. Previous studies indicate that CD147 is involved in the progression of chemotherapy resistance in breast cancer and ovarian cancer cells and its expression is negative regulated by miR-492 in muscles cells. In the present study, we found that lower level of miR-492 is accompanied with increased expression of CD147 in Oxaliplatin-resistant colon cancer cell line LS174T/L-OHP as compared with its parental cell line LS174T. Exogenous expression of miR-492 in LS174T/L-OHP could sensitize its reaction on the treatment of Oxaliplatin, which is coincided with its directly reducing the expression of CD147. Furthermore, we found that knockdown of CD147 in LS174T/L-OHP could also sensitize its reaction of the treatment with Oxaliplatin. Besides, intratumoral delivering of miR-492 could also restore Oxaliplatin treatment response in Oxaliplatin-resistant xenografts in vivo. These findings provide direct evidences that the miR-492/CD147 axis might play an essential role in the Oxaliplatin resistance of colon cancer cells, suggesting that the miR-492/CD147 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in colon cancer.

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Acknowledgments

This work was funded by the Shandong Provincial Foundation for Natural Sciences (ZR2011HM07).

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    Authors and Affiliations

    1. Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China

      Lipan Peng, Jinshen Wang, Honglai Zhang, Changqing Jin, Leping Li, Tao Xu & Ruizheng Miao

    2. Department of Breast Surgery, Qingdao municipal hospital, Qingdao, People’s Republic of China

      Huaqiang Zhu

    3. Department of Radiotherapy, Shandong Cancer Hospital, Jinan, People’s Republic of China

      Haina Sui

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    1. Lipan Peng
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    2. Huaqiang Zhu
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    3. Jinshen Wang
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    4. Haina Sui
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    5. Honglai Zhang
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    6. Changqing Jin
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    7. Leping Li
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    8. Tao Xu
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    9. Ruizheng Miao
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    Correspondence to Ruizheng Miao.

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    Lipan Peng and Tongxing Cui have contributed equally to this work.

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    Peng, L., Zhu, H., Wang, J. et al. MiR-492 is functionally involved in Oxaliplatin resistance in colon cancer cells LS174T via its regulating the expression of CD147. Mol Cell Biochem 405, 73–79 (2015). https://doi.org/10.1007/s11010-015-2397-z

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    • DOI: https://doi.org/10.1007/s11010-015-2397-z

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