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The roles of miR-200c in colon cancer and associated molecular mechanisms

Tumor Biology volume 35, pages 6475–6483 (2014)Cite this article

Abstract

The expression of miR-200c has been widely reported to be elevated in tumor tissues and sera of patients with colorectal cancer (CRC) and has been found to correlate with poor prognosis. However, how miR-200c regulates the apoptosis, survival, invasion, metastasis, and tumor growth in colon cancer cells remains to be fully elucidated. This study seeks to further investigate the role of miR-200c in colon cancer development. The expression of miR-200c in tumor and peritumoral tissues of 101 colon cancer patients was measured by real-time PCR. miR-200c expression in HCT-116 and HT-29 colon cancer cells was silenced by adenovirus-carried expression of antisense mRNA against miR-200c. The protein levels of PTEN, p53 Ser15, PP1, and activated caspase-3 in HCT-116 and HT-29 cells were measured by Western blot. This study demonstrated that the expression of miR-200c was significantly higher in tumor tissues than in peritumoral tissues of colon cancer patients. The elevated miR-200c expression significantly correlated with the TNM stage, lymph node metastasis, and invasion of colon cancer. Silencing miR-200c expression significantly induced cell apoptosis, inhibited long-term survival, invasion, and metastasis, and delayed xenograft tumor growth. Importantly, silencing miR-200c expression sensitized the therapeutic effect of Ara-C (Cytarabine). The effects of silencing miR-200c expression were associated with upregulation of PTEN protein and p53 Ser15 phosphorylation levels in HCT-116 cells and PTEN protein expression in HT-29 cells. In conclusion, miR-200c functions as an oncogene in colon cancer cells through regulating tumor cell apoptosis, survival, invasion, and metastasis as well as xenograft tumor growth through inhibition of PTEN expression and p53 phosphorylation.

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Affiliations

  1. Hepatobiliary and Enteric Surgery Research Center Xiangya Hospital, Central South University, Changsha, 410008, China

    Jianmei Chen, Yangde Zhang, Tiehui Hu & Yuxiang Chen

  2. Department of Gastroenterology, First Hospital of Changsha City, Changsha, 410008, China

    Weining Wang

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  1. Jianmei Chen
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  2. Weining Wang
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Correspondence to Yuxiang Chen.

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Chen, J., Wang, W., Zhang, Y. et al. The roles of miR-200c in colon cancer and associated molecular mechanisms. Tumor Biol. 35, 6475–6483 (2014). https://doi.org/10.1007/s13277-014-1860-x

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  • DOI: https://doi.org/10.1007/s13277-014-1860-x

Keywords

  • Colon cancer
  • miR-200c
  • Apoptosis
  • Metastasis
  • PTEN
  • p53
  • PP1