Oncotarget

Research Papers:

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

Yulong Shang, Bin Feng, Lin Zhou, Gui Ren, Zhiyong Zhang, Xing Fan, Yi Sun, Guanhong Luo, Jie Liang, Kaichun Wu, Yongzhan Nie and Daiming Fan _

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Oncotarget. 2016; 7:538-549. https://doi.org/10.18632/oncotarget.6374

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Abstract

Yulong Shang1,*, Bin Feng1,*, Lin Zhou2,*, Gui Ren1, Zhiyong Zhang1, Xing Fan3, Yi Sun4, Guanhong Luo1, Jie Liang1, Kaichun Wu1, Yongzhan Nie1, Daiming Fan1

1State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China

2The 88th Hospital of PLA, Tai’an 271001, China

3Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China

4Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710032, China

*These authors have contributed equally to this work

Correspondence to:

Daiming Fan, e-mail: [email protected]

Yongzhan Nie, e-mail: [email protected]

Keywords: gastric cancer, multidrug resistance, miR-27b, miR-508-5p, CCNG1

Received: May 03, 2015     Accepted: November 13, 2015     Published: November 23, 2015

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.


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