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作 者:Zhe-Min Lin Dong-Dong Fan Song Jin Zhan-Liang Liu Yi-Nong Niu
机构地区:[1]Department of Urology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100016,China [2]Department of Urology,Beijing Miyun Teaching Hospital,Capital Medical University,Beijing 101500,China [3]Department of Urology,Beijing Tsinghua Changgung Hospital,Tsinghua University,Beijing 102218,China
出 处:《Asian Journal of Andrology》2021年第3期266-272,共7页亚洲男性学杂志(英文版)
基 金:the National Natural Science Foundation of China(No.81770754);the Beiing Natural Science Foundation(No.7172081)at Beijing Chaoyang Hospital,Capital Medical University,through funding provided to YNN.
摘 要:The inhibition of 5-a reductase type 2(SRD5A2)by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement(BPE).Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy.Our previous work showed that methylated cytosine-phosphate-guanine(CpG)islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression.Here,we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein(scored 0-100)occurred in 10.0%(4/40)of benign adult prostates.We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1(DNMT1)expression.In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment,and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2T-deoxycytidine(5-Aza-CdR)or N-phthalyl-L-tryptophan(RG108).Furthermore,we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis.Ten methylated CpG dinucleotides,including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon,were found in a CpG island located from-400 bp to+600 bp in SRD5A2,which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression.Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2,which may partially account for the resistance to finasteride observed in certain BPE patients.
关 键 词:5-a reductase benign prostatic enlargement CpG island methylated CpG dinucleotides METHYLATION
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