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miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1

Oncogene volume 33, pages 3267–3276 (2014)Cite this article

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Abstract

Multidrug resistance (MDR) is usually correlated with the poor prognosis of gastric cancer. In this study, we revealed a total of 11 microRNAs (miRNA) that regulated MDR of gastric cancer via high-throughput functional screening, and miR-508-5p reversed MDR most efficiently among these candidate miRNAs. The overexpression of miR-508-5p was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitize tumours to chemotherapy in vivo. Further studies showed that miR-508-5p could directly target the 3′-untranslated regions of ABCB1 and Zinc ribbon domain-containing 1 (ZNRD1), and suppress their expression at the mRNA and protein levels. Meanwhile, the suppression of ZNRD1 led to a decrease in ABCB1. These findings suggest that a miR-508-5p/ZNRD1/ABCB1 regulatory loop has a critical role in MDR in gastric cancer. In addition, miR-508-5p could be used as a prognostic factor for overall survival in gastric cancer. These data reveal an important role for miR-508-5p in the regulation of MDR in gastric cancer, and suggest the potential application of miR-508-5p in drug resistance prediction and treatment.

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Acknowledgements

This work was supported by grants 81030044, 2010CB529300, 2010CB529305, 06, 02, NSFC-81120108005, 81172096 and 863-2012AA02A203. We would like to thank Zheng Chen and Jianhua Dou from the Fourth Military Medical University for providing excellent technical assistance.

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  1. Y Shang, Z Zhang and Z Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, Xi’an, China

    Y Shang, Z Zhang, Z Liu, B Feng, G Ren, K Li, L Zhou, Y Sun, M Li, J Zhou, K Wu, Y Nie & D Fan

  2. Department of General Surgery, General Hospital of Jinan Military Command, Jinan, China

    Y An

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Shang, Y., Zhang, Z., Liu, Z. et al. miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene 33, 3267–3276 (2014). https://doi.org/10.1038/onc.2013.297

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