MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells

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Date
2016-02-15
Authors
Nyhan, Michelle J.
O'Donovan, Tracey R.
Boersma, Antonius W. M.
Wiemer, Erik A. C.
McKenna, Sharon L.
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BioMed Central
Published Version
10.1186/s12885-016-2123-6
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Abstract
Background: Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal. Methods: MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells. Results: MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines with higher expression in chemosensitive apoptosis inducing cell lines. Colony formation assays showed that overexpression of miR-193b significantly impedes the ability of KYSE450 cells to recover following 5-fluorouracil (5-FU) treatment. The critical mRNA targets of miR-193b are unknown but target prediction and siRNA data analysis suggest that it may mediate some of its effects through stathmin 1 regulation. Apoptosis was not involved in the enhanced cytotoxicity. Overexpression of miR-193b in these cells induced autophagic flux and non-apoptotic cell death. Conclusion: These results highlight the importance of miR-193b in determining oesophageal cancer cell viability and demonstrate an enhancement of chemotoxicity that is independent of apoptosis induction.
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Keywords
MiR-193b Autophagy , Chemosensitivity , Stathmin 1 , Oesophageal cancer , Non-apoptotic cell death
Citation
Nyhan, M. J., O’Donovan, T. R., Boersma, A. W. M., Wiemer, E. A. C. and McKenna, S. L. (2016) 'MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells', BMC Cancer, 16(1), pp. 101. doi:10.1186/s12885-016-2123-6
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https://hdl.handle.net/10468/3686
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Cancer Research @ UCC - Journal Articles
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© 2016 Nyhan et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.