Epigenetic inactivation of the hsa-miR-203 in haematological malignancies.
Epigenetic inactivation of the hsa-miR-203 in haematological malignancies.
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血液恶性肿瘤中 hsa-miR-203 的表观遗传失活。
DOI：
10.1111/j.1582-4934.2011.01274.x
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发表时间：
2011-12
影响因子：
5.3
通讯作者：
Yu L
中科院分区：
文献类型：
--
作者：
Chim CS;Wong KY;Leung CY;Chung LP;Hui PK;Chan SY;Yu L
miR-203是一种肿瘤抑制microRNA（miRNA）。我们通过甲基化特异性PCR研究了150例样本中hsa-miR-203的甲基化，包括急性髓性白血病（AML），急性淋巴细胞白血病（ALL），慢性髓性白血病（CML），慢性淋巴细胞白血病（CLL）和非霍奇金淋巴瘤（NHL），并通过茎环RT-qPCR研究了miRNA表达。正常对照组hsa-miR-203启动子未甲基化，但在2株AML和4株淋巴瘤细胞系中均发生甲基化，其中5-Aza-2′-deoxycytidine处理导致启动子去甲基化和miR-203重新表达。淋巴瘤细胞中miR-203表达的恢复抑制了细胞增殖并增加了细胞死亡，表明了固有的肿瘤抑制活性。在原代样本中，CML中不存在hsa-miR-203甲基化，但在5.0%的ALL、10.0%的AML、42.0%的CLL和38.8%的NHL（包括6个[60.0%]天然巨噬细胞、9个[40.9%] B细胞和4个[23.5%] T细胞NHL）中检测到。此外，在NHL中，hsa-miR-203甲基化与hsa-miR-34 a、-124 a和-196 b的高甲基化相关，而在CLL中则无关。在CLL中，hsa-miR-203甲基化与较高的呈现Hb水平相关（P = 0.033）。CLL患者的预计10年总生存率为58.2%，这受到Rai分期和高风险核型的影响，但不受hsa-miR-203甲基化的影响。hsa-miR-203在淋巴系恶性肿瘤中甲基化的频率高于髓系恶性肿瘤（P = 0.002）。总之，肿瘤抑制基因miR-203以肿瘤特异性方式高甲基化，基因沉默。hsa-miR-203在淋巴系统恶性肿瘤中的高甲基化频率高于髓系恶性肿瘤。在NHL中，hsa-miR-203甲基化与其他肿瘤抑制miRNA的伴随甲基化相关。hsa-miR-203甲基化在淋巴系统恶性肿瘤中的频繁发生提示hsa-miR-203甲基化的致病作用。
miR-203 is a tumour suppressor microRNA (miRNA). We studied the methylation of hsa-miR-203 in 150 samples including acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL) and non-Hodgkin’s lymphoma (NHL) by methylation-specific PCR, and miRNA expression by stem-loop RT-qPCR. hsa-miR-203 promoter was unmethylated in normal controls but homozygously methylated in two AML and four lymphoma cell lines, in which 5-Aza-2′-deoxycytidine treatment led to promoter demethylation and miR-203 re-expression. Restoration of miR-203 expression in lymphoma cells inhibited cellular proliferation and increased cell death, suggesting an inherent tumour suppressor activity. In primary samples, hsa-miR-203 methylation was absent in CML but detected in 5.0% ALL, 10.0% AML, 42.0% CLL and 38.8% of NHL (including six [60.0%] natural killer-cell, nine [40.9%] B-cell and four [23.5%] T cell NHL). Moreover, hsa-miR-203 methylation was associated with hypermethylation of hsa-miR-34a, -124a and -196b in NHL but not CLL. In CLL, hsa-miR-203 methylation was associated with a higher presenting Hb level (P = 0.033). The projected 10 year overall survival of the CLL patients was 58.2%, which was impacted by Rai stage and high-risk karyotypes but not hsa-miR-203 methylation. hsa-miR-203 was more frequently methylated in lymphoid than myeloid malignancies (P = 0.002). In conclusion, miR-203, a tumour suppressor gene, was hypermethylated in a tumour-specific manner with gene silencing. hsa-miR-203 was more frequently hypermethylated in lymphoid than myeloid malignancies. In NHL, hsa-miR-203 methylation was associated with concomitant methylation of other tumour suppressor miRNAs. The frequent hsa-miR-203 methylation in lymphoid malignancies suggested a pathogenetic role of hsa-miR-203 methylation.
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影响因子：
20.3
作者：
Chim, CS;Fung, TK;Kwong, YL
通讯作者：
Kwong, YL
影响因子：
20.3
作者：
Chim, CS;Ma, SY;Kwong, YL
通讯作者：
Kwong, YL
影响因子：
4.7
作者：
Chim, C. S.;Wong, K. Y.;Liang, R.
通讯作者：
Liang, R.
影响因子：
3.5
作者：
Chim, CS;Wong, ASY;Kwong, YL
通讯作者：
Kwong, YL
影响因子：
12.8
作者：
Chim, CS;Wong, ASY;Kwong, YL
通讯作者：
Kwong, YL