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miRNA-183 Suppresses Apoptosis and Promotes Proliferation in Esophageal Cancer by Targeting PDCD4

  • Yang, Miao (Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University) ;
  • Liu, Ran (Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University) ;
  • Li, Xiajun (Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University) ;
  • Liao, Juan (Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University) ;
  • Pu, Yuepu (Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University) ;
  • Pan, Enchun (Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University) ;
  • Yin, Lihong (Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University) ;
  • Wang, Yi (Huaian Center for Disease Control and Prevention)
  • Received : 2014.06.05
  • Accepted : 2014.09.22
  • Published : 2014.12.31

Abstract

In our previous study, miRNA-183, a miRNA in the miR-96-182-183 cluster, was significantly over-expressed in esophageal squamous cell carcinoma (ESCC). In the present study, we explored the oncogenic roles of miR-183 in ESCC by gain and loss of function analysis in an esophageal cancer cell line (EC9706). Genome-wide mRNA micro-array was applied to determine the genes that were regulated directly or indirectly by miR-183. 3'UTR luciferase reporter assay, RT-PCR, and Western blot were conducted to verify the target gene of miR-183. Cell culture results showed that miR-183 inhibited apoptosis (p < 0.05), enhanced cell proliferation (p < 0.05), and accelerated G1/S transition (p < 0.05). Moreover, the inhibitory effect of miR-183 on apoptosis was rescued when miR-183 was suppressed via miR-183 inhibitor (p < 0.05). Western blot analysis showed that the expression of programmed cell death 4 (PDCD4), which was predicted as the target gene of miR-183 by microarray profiling and bioinformatics predictions, decreased when miR-183 was over-expressed. The 3'UTR luciferase reporter assay confirmed that miR-183 directly regulated PDCD4 by binding to sequences in the 3'UTR of PDCD4. Pearson correlation analysis further confirmed the significant negative correlation between miR-183 and PDCD4 in both cell lines and in ESCC patients. Our data suggest that miR-183 might play an oncogenic role in ESCC by regulating PDCD4 expression.

Keywords

References

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