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Oncogene. 2014 Jun 19;33(25):3267-76. doi: 10.1038/onc.2013.297. Epub 2013 Jul 29.

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

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  • 1State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
  • 2Department of General Surgery, General Hospital of Jinan Military Command, Jinan, China.


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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