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Mir-148a Improves Response to Chemotherapy in Sensitive and Resistant Oesophageal Adenocarcinoma and Squamous Cell Carcinoma Cells

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Response to chemotherapy varies widely in patients with advanced oesophageal cancer. We investigated the impact of manipulating certain microRNAs on response to cisplatin and 5-fluorouracil (5-FU) in oesophageal cancer cells.

Methods

Cisplatin-/5-fluorouracil-resistant oesophageal squamous cell carcinoma (SCC) and adenocarcinoma (EAC) cell lines were established, and the impact of ectopic upregulation of miR-106a and miR-148a on response to both drugs was assessed.

Results

The impact of miR-106a-upregulation was inconsistent. Upregulation was followed by reduced sensitivity to cisplatin in chemotherapy-sensitive EAC cells (cell survival, +8.7 ± 0.8%; p = 0.003) and an improved response to 5-FU in cisplatin-resistant EAC cells (cell survival, −6.4 ± 2.5%; p = 0.011). MiR-148a upregulation significantly increased sensitivity to chemotherapy in seven out of ten cell lines, represented by a decrease in cell viability of 22.6 ± 7.9% to 50.5 ± 10.6% after cisplatin (p ≤ 0.014) and 6.0 ± 0.8% to 15.0 ± 4.1% after 5-FU treatment (p ≤ 0.012). The only cell lines in which miR-148a upregulation had no effect were cisplatin-resistant EAC exposed to cisplatin and 5-FU-sensitive and 5-FU-resistant SCC cells exposed to 5-FU.

Conclusion

MiR-148a sensitized chemotherapy-sensitive oesophageal cancer cell lines to cisplatin and, to a lesser extent, to 5-flurouracil and attenuated resistance in chemotherapy-resistant variants. Further experimental and clinical studies to investigate the exact mechanisms involved are warranted.

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Acknowledgments

We thank Prof. Dr. M Bruewer for his support in planning and performing the current study. Dr Richard Hummel was supported by a Research Fellowship of the German Research Foundation (DFG) to R.H. (Hu 1763/1-1). Funding was also obtained from a project grant from the National Health and Medical Research Council of Australia (grant no. 595964).

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Authors and Affiliations

  1. Department of Surgery, Flinders University, Room 3D213, Flinders Medical Centre, 5042, Bedford Park, South Australia, Australia

    Richard Hummel, David I. Watson, Cameron Smith, Jakob Kist & Damian J. Hussey

  2. Gastroenterology & Hepatology, Flinders University, 5042, Bedford Park, South Australia, Australia

    Michael Z. Michael

  3. Department of General and Visceral Surgery, University of Muenster, Waldeyerstrasse 1, Muenster, Germany

    Richard Hummel

  4. Comprehensive Cancer Centre, University of Muenster, Waldeyerstrasse 1, Muenster, Germany

    Joerg Haier

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  1. Richard Hummel
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Correspondence to Richard Hummel.

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Statement

Part of the results reported in this paper have been presented at the 12th World Congress of the International Society for Diseases of the Esophagus, Japan, September 2010, and published in abstract form as: Impact of miRNAs on sensitivity to anticancer treatment in sensitive and resistant esophageal squamous cell carcinoma cell lines. Dis Esophagus. 2010 Aug;23 Suppl 1:48A-49A

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Hummel, R., Watson, D.I., Smith, C. et al. Mir-148a Improves Response to Chemotherapy in Sensitive and Resistant Oesophageal Adenocarcinoma and Squamous Cell Carcinoma Cells. J Gastrointest Surg 15, 429–438 (2011). https://doi.org/10.1007/s11605-011-1418-9

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