Journal
ONCOGENE
Volume 33, Issue 25, Pages 3267-3276Publisher
SPRINGERNATURE
DOI: 10.1038/onc.2013.297
Keywords
miR-508-5p; gastric cancer; drug resistance; ABCB1; ZNRD1
Funding
- [81030044]
- [2010CB529300]
- [2010CB529305]
- [2010CB529306]
- [2010CB529302]
- [NSFC-81120108005]
- [81172096]
- [863-2012AA02A203]
- [8632012AA02A504]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available