Woo Yu Mi, Shin Yubin, Hwang Jung-Ah, Hwang Young-Hwan, Lee Sunyoung, Park Eun Young, Kong Hyun Kyung, Park Hayne Cho, Lee Yeon-Su, Park Jong Hoon
Department of Biological Science, Sookmyung Women's University, Seoul, 140-742, Korea.
Branch of Cancer Genomics, Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
Sci Rep. 2015 Oct 14;5:15238. doi: 10.1038/srep15238.
Although autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease, and is characterized by the formation of multiple fluid-filled cysts, which results in renal failure, early diagnosis and treatment of ADPKD have yet to be defined. Herein, we observed that the promoter region of the gene encoding mucin-like protocadherin (MUPCDH) was hypermethylated in the renal tissue of patients with ADPKD compared to non-ADPKD controls. Inversely, MUPCDH was significantly repressed in ADPKD, especially in cyst-lining cells. Our results indicate that aberrant methylation of MUPCDH promoter CpG islands may be negatively correlated with reduced expression level of MUPCDH and that this contributes to abnormal cell proliferation in ADPKD. It suggests that methylation status of MUPCDH promoter can be used as a novel epigenetic biomarker and a therapeutic target in ADPKD.
尽管常染色体显性多囊肾病(ADPKD)是一种常见的遗传病,其特征是形成多个充满液体的囊肿,最终导致肾衰竭,但ADPKD的早期诊断和治疗方法尚未明确。在此,我们观察到,与非ADPKD对照相比,编码黏蛋白样原钙黏蛋白(MUPCDH)的基因启动子区域在ADPKD患者的肾组织中发生了高甲基化。相反,MUPCDH在ADPKD中显著受抑制,尤其是在囊肿衬里细胞中。我们的结果表明,MUPCDH启动子CpG岛的异常甲基化可能与MUPCDH表达水平降低呈负相关,并且这促成了ADPKD中的异常细胞增殖。这表明MUPCDH启动子的甲基化状态可作为ADPKD中一种新的表观遗传生物标志物和治疗靶点。