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Downregulation of EphA5 by promoter methylation in human prostate cancer

Overview of attention for article published in BMC Cancer, January 2015
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Title
Downregulation of EphA5 by promoter methylation in human prostate cancer
Published in
BMC Cancer, January 2015
DOI 10.1186/s12885-015-1025-3
Pubmed ID
Authors

Shibao Li, Yingfeng Zhu, Chunguang Ma, Zhenhua Qiu, Xinju Zhang, Zhihua Kang, Zhiyuan Wu, Hua Wang, Xiao Xu, Hu Zhang, Guoqiang Ren, Jianmin Tang, Xiangyu Li, Ming Guan

Abstract

BackgroundEphA5 is a member of the Eph/ephrin family and plays a critical role in the regulation of carcinogenesis. A significant reduction of EphA5 transcripts in high-grade prostate cancer tissue was shown using a transcriptomic analysis, compared to the low-grade prostate cancer tissue. As less is known about the mechanism of EphA5 downregulation and the function of EphA5, here we investigated the expression and an epigenetic change of EphA5 in prostate cancer and determined if these findings were correlated with clinicopathologic characteristics of prostate cancer.MethodsSeven prostate cell lines (RWPE-1, LNCap, LNCap-LN3, CWR22rv-1, PC-3, PC-3M-LN4, and DU145),thirty-nine BPH, twenty-two primary prostate carcinomas, twenty-three paired noncancerous and cancerous prostate tissues were examined via qRT-PCR, methylation-specific PCR, bisulfite sequencing, immunohistochemistry and western blotting. The role of EphA5 in prostate cancer cell migration and invasion was examined by wound healing and transwell assay.ResultsDownregulation or loss of EphA5 mRNA or protein expression was detected in 28 of 45 (62.2%) prostate carcinomas, 2 of 39 (5.1%) hyperplasias, and all 6 prostate cancer cell lines. Methylation of the EphA5 promoter region was present in 32 of 45 (71.1%) carcinoma samples, 3 of 39 (7.7%) hyperplasias, and the 6 prostate cancer cell lines. Among 23 paired prostate carcinoma tissues, 16 tumor samples exhibited the hypermethylation of EphA5, and 15 of these 16 specimens (93.8%) shown the downregulation of EphA5 expression than that of their respectively matched noncancerous samples. Immunostaining analysis demonstrated that the EphA5 protein was absent or down-regulated in 10 of 13 (76.9%) available carcinoma samples, and 8 of these 10 samples (80.0%) exhibited hypermethylation. The frequency of EphA5 methylation was higher in cancer patients with an elevated Gleason score or T3-T4 staging. Following the treatment of 6 prostate cancer cell lines with 5-aza-2¿-deoxycytidine, the levels of EphA5 mRNA were significantly increased. Prostate cancer cells invasion and migration were significantly suppressed by ectopic expression of EphA5 in vitro.ConclusionOur study provides evidence that EphA5 is a potential target for epigenetic silencing in primary prostate cancer and is a potentially valuable prognosis predictor and thereapeutic marker for prostate cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 26%
Student > Bachelor 6 14%
Student > Postgraduate 5 12%
Student > Master 5 12%
Student > Doctoral Student 2 5%
Other 5 12%
Unknown 9 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 26%
Agricultural and Biological Sciences 8 19%
Medicine and Dentistry 7 16%
Unspecified 2 5%
Mathematics 1 2%
Other 2 5%
Unknown 12 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 January 2015.
All research outputs
#18,389,490
of 22,778,347 outputs
Outputs from BMC Cancer
#5,421
of 8,288 outputs
Outputs of similar age
#255,910
of 351,834 outputs
Outputs of similar age from BMC Cancer
#93
of 132 outputs
Altmetric has tracked 22,778,347 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
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