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Oncotarget. 2016 Jul 19;7(29):45302-45316. doi: 10.18632/oncotarget.9605.

EGR1 mediates miR-203a suppress the hepatocellular carcinoma cells progression by targeting HOXD3 through EGFR signaling pathway.

Author information

1
Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P.R. China.
2
Department of Pathology, Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, P.R. China.
3
Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P.R. China.
4
Cardiovascular Research Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P.R. China.

Abstract

EGR1 plays a critical role in cancer progression. However, its precise role in hepatocellular carcinoma has not been elucidated. In this study, we found that the overexpression of EGR1 suppresses hepatocellular carcinoma cell proliferation and increases cell apoptosis by binding to the miR-203a promoter sequence. In addition, we investigated the function of miR-203a on progression of HCC cells. We verified that the effect of overexpression of miR-203a is consistent with that of EGR1 in regulation of cell progression. Through bioinformatic analysis and luciferase assays, we confirmed that miR-203a targets HOXD3. Silencing HOXD3 could block transition of the G2/M phase, increase cell apoptosis, decrease the expression of cell cycle and apoptosis-related proteins, EGFR, p-AKT, p-ERK, CCNB1, CDK1 and Bcl2 by targeting EGFR through EGFR/AKT and ERK cell signaling pathways. Likewise, restoration of HOXD3 counteracted the effects of miR-203a expression.In conclusion, our findings are the first to demonstrate that EGR1 is a key player in the transcriptional control of miR-203a, and that miR-203a acts as an anti-oncogene to suppress HCC tumorigenesis by targeting HOXD3 through EGFR-related cell signaling pathways.

KEYWORDS:

EGR1; HOXD3; cell progression; hepatocellular carcinoma; miR-203a

PMID:
27244890
PMCID:
PMC5216724
DOI:
10.18632/oncotarget.9605
[Indexed for MEDLINE]
Free PMC Article

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