关键词: 甲基化特异性PCR, 亚硫酸盐测序PCR, 前列腺癌, 癌高甲基化基因1, 甲基化

Abstract: Background and purpose: Hypermethylated in cancer 1 (HIC1) is silenced in multiple cancer cells and tissues by DNA methylation of epigenetic modification, which may modulate the initiation and progression of tumors. However, there are few reports about this phenomenon in prostate cancer. This study aimed to investigate the status of HIC1 promoter methylation in prostate cancer using methylation methods. Methods: Methylation-specific polymerase chain reaction (MSP) and bisulfate sequencing PCR (BSP) were used to detect the methylation status of HIC1 promoter in prostate cancer cell lines PC3 and C4-2B, prostate normal cell line PrEC, primary Chinese PCa tissues and the respective healthy control cases. HIC1 expression level was respectively determined by reverse transcription-PCR (RT-PCR) and Western blot assays in PC3, C4-2B and PrEC cells treated with 5-Aza-CdR. Results: We found that the percentages of HIC1 promoter methylation were 78.23%, 72.15% and 10.63% in PC3, C4-2B and PrEC cells by MSP analyses. Moreover, the levels of methylated HIC1 promoter in 36 primary Chinese PCa tissues compared with the respective healthy control cases were 80.30% vs 31.56%. Expressions of HIC1 mRNA and protein level were restored in PC3 and C4-2B cells after 5-Aza-CdR treatment. Conclusion: These findings demonstrate that HIC1 promoter region is hypermethylated in prostate cancer, which results in silence or downregulation of HIC1. The status of HIC1 methylation can be a valuable marker in the early stage of prostate cancer and a potential therapeutic target.

Key words: Methylation specific PCR, Bisulfate sequencing PCR, Prostate cancer, Hypermethylated in cancer 1, Methylation