ABSTRACT
Objective To explore promoter methylation of HIC1 gene and the expression of HIC1/SIRT1 related to the occurrence, development, and metastasis of papillary thyroid carcinoma. Methods Using Bisulfite sequencing PCR to analyze the promoter methylation of HIC1 gene. Using quantitative real-time PCR and Western blot to analyze expression differences of HIC1 and SIRT1 genes in tissues of papillary thyroid carcinoma(40 cases) and in adjacent normal thyroid(40 cases), of which datas were analyzed by statistics. Results The degree of HIC1 gene promoter methylation was significantly higher than that in adjacent normal tissues(P<0. 01). The degree of HIC1 gene promoter methylation in papillary thyroid carcinoma was related to lymph node metastasis, age, and the tumor-node-metastasis stages(P<0. 01). Compared with the expression of HIC1 mRNA and protein in adjacent normal thyroid tissue, that in papillary thyroid carcinoma was significantly lower(P<0. 01), while the expression of SIRT1 mRNA and protein in papillary thyroid carcinoma was significantly higher(P<0. 01). The lower expression of HIC1 mRNA and protein in the tumor tissues was related to the stage of lymph node metastasis, age, and the tumor-node-metastasis stages(P<0. 05). There was a strong negative correlation between the degree of HIC1 gene promoter methylation and expression of HIC1 in papillary thyroid carcinoma(P<0. 05). The expression of HIC1 mRNA and protein between that of SIRT1 also showed a strong negative correlation(P<0. 01). Conclusion Promoter hypermethylation of HIC1 and aberrant expression of HIC1/SIRT1 in papillary thyroid carcinoma may play a significant role in the oncogenesis and progress of papillary thyroid carcinoma. HIC1 is expected to become a new marker for prevention and treatment of papillary thyroid carcinoma.
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 ofHIC1 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 methylatedHIC1 promoter in 36 primary Chinese PCa tissues compared with the respective healthy control cases were 80.30%vs 31.56%. Expressions ofHIC1 mRNA and protein level were restored in PC3 and C4-2B cells after 5-Aza-CdR treatment.Conclusion:These findings demonstrate thatHIC1 promoter region is hypermethylated in prostate cancer, which results in silence or downregulation ofHIC1. The status ofHIC1 methylation can be a valuable marker in the early stage of prostate cancer and a potential therapeutic target.