Dataset Information

The miR27b-CCNG1-P53-miR-508-5p axis regulates multidrug resistance of gastric cancer.

ABSTRACT: Multidrug resistance (MDR) correlates with treatment failure and poor prognosis among gastric cancer (GC) patients. In a previous study using high-throughput functional screening, we identified 11 microRNAs (miRNAs) that regulate MDR in GC and found that miR-508-5p reversed MDR by targeting ABCB1 and ZNRD1. However, the mechanism by which miR-508-5p was decreased in chemo-resistant GC cells was unclear. In this study, we found that ectopic miR-27b is sufficient to sensitize tumors to chemotherapy in vitro and in vivo. Moreover, miR-27b directly targets the 3' untranslated regions (3'-UTRs) of CCNG1, a well-known negative regulator of P53 stability. Interestingly, miR-27b up-regulation leads to increased miR-508-5p expression, and this phenomenon is mediated by CCNG1 and P53. Further investigation indicated that miR-508-5p is directly regulated by P53. Thus, the miR-27b/CCNG1/P53/miR-508-5p axis plays important roles in GC-associated MDR. In addition, miR-27b and miR-508-5p expression was detected in GC tissues with different chemo-sensitivities, and we found that tissues in which miR-27b and miR-508-5p are up-regulated are more sensitive to chemotherapy. Together, these data suggest that the combination of miR-27b and miR-508-5p represents a potential marker of MDR. Restoring the miR-27b and miR-508-5p levels might contribute to MDR reversion in future clinical practice.

SUBMITTER: Shang Y

PROVIDER: S-EPMC4808016 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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The miR27b-CCNG1-P53-miR-508-5p axis regulates multidrug resistance of gastric cancer.

Shang Yulong Y Feng Bin B Zhou Lin L Ren Gui G Zhang Zhiyong Z Fan Xing X Sun Yi Y Luo Guanhong G Liang Jie J Wu Kaichun K Nie Yongzhan Y Fan Daiming D

Oncotarget 20160101 1

Multidrug resistance (MDR) correlates with treatment failure and poor prognosis among gastric cancer (GC) patients. In a previous study using high-throughput functional screening, we identified 11 microRNAs (miRNAs) that regulate MDR in GC and found that miR-508-5p reversed MDR by targeting ABCB1 and ZNRD1. However, the mechanism by which miR-508-5p was decreased in chemo-resistant GC cells was unclear. In this study, we found that ectopic miR-27b is sufficient to sensitize tumors to chemotherap ...[more]

PMID: 26623719

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The miR27b-CCNG1-P53-miR-508-5p axis regulates multidrug resistance of gastric cancer.

Publications

The miR27b-CCNG1-P53-miR-508-5p axis regulates multidrug resistance of gastric cancer.

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