Molecular and Cellular Biochemistry

, Volume 357, Issue 1–2, pp 31–38 | Cite as

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

  • Jian Li
  • Yangde Zhang
  • Jingfeng Zhao
  • Fangren Kong
  • Yuxiang Chen


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.


Colon cancer Chemoresistance miRNA Apoptosis Paclitaxel 



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


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Jian Li
    • 1
    • 2
  • Yangde Zhang
    • 1
  • Jingfeng Zhao
    • 2
  • Fangren Kong
    • 3
  • Yuxiang Chen
    • 1
  1. 1.Hepatobiliary & Enteric Surgery Research CenterCentral South UniversityChangshaChina
  2. 2.Xiangya HospitalCentral South UniversityChangshaChina
  3. 3.Cancer Research InstituteCentral South UniversityChangshaChina

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