[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.14348/molcells.2014.0147

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)

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

apoptosis; esophageal cancer; miR-183; PDCD4; proliferation;

Citations & Related Records

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