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miR-33a suppresses the nuclear translocation of β-catenin to enhance gemcitabine sensitivity in human pancreatic cancer cells

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Tumor Biology

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, partly due to its high level of drug resistance. β-Catenin is critical for drug resistance in pancreatic cancer, which occurs through multiple mechanisms. Here, we observed that miR-33a targeted the 3′UTR of β-catenin, inducing apoptosis and inhibiting the growth of human pancreatic cancer cells. Moreover, gemcitabine (GEM) treatment enhanced β-catenin expression by reducing miR-33a expression in a dose-dependent manner. GEM-resistant MiaPaCa-2res cells with a low level of miR-33a expression and high level of β-catenin expression adopted spindle-shaped morphologies, similar to their morphologies during the epithelial-to-mesenchymal transition (EMT), and their normal morphologies were restored by miR-33a overexpression. Furthermore, miR-33a downregulated β-catenin nuclear translocation, decreasing the transcription of survivin, cyclin D1, and MDR-1, and the protein expression of slug, vimentin, and N-cadherin, thereby mediating sensitization to GEM. Thus, miR-33a might function as a tumor suppressor to downregulate β-catenin expression, affecting cell growth, apoptosis, the EMT, and GEM resistance.

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Acknowledgments

This work was supported in part by the National Science Foundation of China (NSFC) (30973476, 81272727, and 81472223).

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This article is distributed under the terms of the Creative Commons Attribution License, which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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Authors and Affiliations

  1. Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, 200032, China

    Chen Liang, Zhen Wang, Ying-Yi Li & Fei Zhang

  2. Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Bao-Hua Yu

  3. Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, 110084, Liaoning, China

    Hong-Yu Li

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  1. Chen Liang
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  2. Zhen Wang
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  3. Ying-Yi Li
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  4. Bao-Hua Yu
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  5. Fei Zhang
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Correspondence to Ying-Yi Li or Hong-Yu Li.

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Liang, C., Wang, Z., Li, YY. et al. miR-33a suppresses the nuclear translocation of β-catenin to enhance gemcitabine sensitivity in human pancreatic cancer cells. Tumor Biol. 36, 9395–9403 (2015). https://doi.org/10.1007/s13277-015-3679-5

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  • DOI: https://doi.org/10.1007/s13277-015-3679-5

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