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Overexpression of miR-22 reverses paclitaxel-induced chemoresistance through activation of PTEN signaling in p53-mutated colon cancer cells

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Abstract

Chemoresistance is a key cause of treatment failure in colon cancer. MiR-22 is a tumor-suppressing microRNA. To explore whether miR-22 is an important player in the development of chemoresistance in colon cancer, we overexpressed miR-22 and subsequently tested its role in cell proliferation, apoptosis, survival, and associated signaling in p53-mutated HT-29 and HCT-15 cells, and p53 wild-type HCT-116 cells. We further investigated the role of miR-22 on cytotoxicity of paclitaxel in both the p53-mutated and p53 wild-type colon cancer cells. Results showed that HT-29 and HCT-15 cells were resistant to paclitaxel-induced cytotoxicity, which normally inhibits cell proliferation and survival, and induces apoptosis. Conversely, HCT-116 was relatively sensitive to the cytotoxicity of paclitaxel. Overexpression of miR-22 significantly decreased cell proliferation and survival, and induced cell apoptosis in the p53-mutated colon cancer cells, but played no role in the p53 wild-type cells. Importantly, miR-22 overexpression enhanced the cytotoxic role of paclitaxel in p53-mutated HT-29 and HCT-15 cells, but not in p53 wild-type HCT-116 cell. We further demonstrated that the tumor-suppressive role of miR-22 in p53-mutated colon cancer cells was mediated by upregulating PTEN expression, which negatively regulated Akt phosphorylation at Ser473 and MTDH expression, and subsequently increased Bax and active caspase-3 levels. Our study is the first to identify the tumor-suppressive role of miR-22 and its associated signaling in the p53-mutated colon cancer cells and highlighted the chemosensitive role of miR-22.

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Acknowledgments

This study was supported by the National Hi-Tech Project of China (Grant Number: AA021810, AA021907 to YC).

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Authors and Affiliations

  1. Hepatobiliary & Enteric Surgery Research Center, Central South University, Changsha, 410008, China

    Jian Li, Yangde Zhang & Yuxiang Chen

  2. Xiangya Hospital, Central South University, Changsha, 410008, China

    Jian Li & Jingfeng Zhao

  3. Cancer Research Institute, Central South University, Changsha, 410008, China

    Fangren Kong

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  1. Jian Li
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  2. Yangde Zhang
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  3. Jingfeng Zhao
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  4. Fangren Kong
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Correspondence to Yuxiang Chen.

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Li, J., Zhang, Y., Zhao, J. et al. Overexpression of miR-22 reverses paclitaxel-induced chemoresistance through activation of PTEN signaling in p53-mutated colon cancer cells. Mol Cell Biochem 357, 31–38 (2011). https://doi.org/10.1007/s11010-011-0872-8

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  • DOI: https://doi.org/10.1007/s11010-011-0872-8

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