CTNNB1 Gene Mutations, Pituitary Transcription Factors, and MicroRNA Expression Involvement in the Pathogenesis of Adamantinomatous Craniopharyngiomas
CTNNB1 Gene Mutations, Pituitary Transcription Factors, and MicroRNA Expression Involvement in the Pathogenesis of Adamantinomatous Craniopharyngiomas
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DOI：
10.1007/s12672-010-0041-7
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发表时间：
2010-08-01
影响因子：
3
通讯作者：
de Castro, Margaret
中科院分区：
文献类型：
--
作者：
Campanini, Marina Lanciotti;Colli, Leandro Machado;de Castro, Margaret
参与腺垂体形成/发育的基因、CTNNB1 基因和 microRNA 可能与颅咽管瘤的发病机制有关。本研究的目的是对 HESX1、PROP1、POU1F1 和 CTNNB1 基因进行分子分析，并评估颅咽管瘤中一组 miRNA 的表达。我们还验证了 CTNNB1 突变的存在是否与临床表现和 miRNA 表达相关。该研究包括 16 名金刚质颅咽管瘤患者（9 名儿童和 7 名成人；8 名女性和 8 名男性；6-55 岁，中位 15.5 岁）。 DNA、RNA 和 cDNA 取自颅咽管瘤和正常垂体。还从健康受试者的外周血中提取了 DNA。所有基因均通过聚合酶链反应扩增并直接测序。使用2(-Delta Delta Ct)方法计算miRNA表达的相对定量。我们发现HESX1、PROP1和POU1F1基因没有突变，PROP1基因有4个多态性，这些多态性处于Hardy-Weinberg平衡状态，并且在颅咽管瘤和对照中具有相似的等位基因频率。我们在 16 名患者中的 8 名中发现了 7 种不同的 CTNNB1 突变。年轻患者比成人更频繁地出现 CTNNB1 突变。我们观察到 miR-150 超表达（1.7 倍）； miR-16-1、miR-21 和 miR23a 的表达无差异；颅咽管瘤中 miR-141、let-7a、miR-16、miR-449、miR-145、miR-143、miR-23b、miR-15a 和 miR-24-2 低表达（范围从 -7.5 至 -2.5 倍；p=0.02）。肿瘤大小或复发与 CTNNB1 突变的存在之间没有关联。 miR-16 和 miR-141 在 CTNNB1 突变的颅咽管瘤中表达不足。 miR-23a 和 miR24-2 在仅接受过一次手术的患者中高表达。与 CTNNB1 突变不同，垂体转录因子的突变或多态性不太可能导致金刚石瘤性颅咽管瘤的发病机制。我们的数据表明 miRNA 表达失调可能参与颅咽管瘤的发病机制和结果，并且 miRNA 可以调节颅咽管瘤肿瘤发生中的 Wnt 信号通路。
Genes involved in formation/development of the adenohypophysis, CTNNB1 gene, and microRNAs might be implicated in the craniopharyngioma pathogenesis. The objective of this study is to perform the molecular analysis of HESX1, PROP1, POU1F1, and CTNNB1 genes and evaluate a panel of miRNA expression in craniopharyngioma. We also verified whether the presence of CTNNB1 mutation is associated with clinical findings and miRNA expression. The study included 16 patients with adamantinomatous craniopharyngioma (nine children and seven adults; eight females and eight males; 6-55 years, median 15.5 years). DNA, RNA, and cDNA were obtained from craniopharyngioma and normal pituitaries. DNA was also extracted from peripheral blood of healthy subjects. All genes were amplified by polymerase chain reaction and direct sequenced. Relative quantification of miRNA expression was calculated using the 2(-Delta Delta Ct) method. We found no mutations in HESX1, PROP1, and POU1F1 genes and four polymorphisms in PROP1 gene which were in Hardy-Weinberg equilibrium and had similar allelic frequencies in craniopharyngioma and controls. We found seven different mutations in CTNNB1 in eight of 16 patients. Younger patients presented more frequently CTNNB1 mutation than adults. We observed hyperexpression of miR-150 (1.7-fold); no different expression of miR-16-1, miR-21, and miR23a; and an underexpression of miR-141, let-7a, miR-16, miR-449, miR-145, miR-143, miR-23b, miR-15a, and miR-24-2 (ranging from -7.5 to -2.5-fold; p=0.02) in craniopharyngioma. There was no association between tumor size or the recurrence and the presence of CTNNB1mutations. miR-16 and miR-141 were underexpressed in craniopharyngioma presenting CTNNB1 mutations. miR-23a and miR24-2 were hyperexpressed in patients who underwent only one surgery. Mutations or polymorphisms in pituitary transcription factors are unlikely to contribute to the adamantinomatous craniopharyngioma pathogenesis, differently of CTNNB1 mutations. Our data suggest the potential involvement of the deregulation of miRNA expression in the craniopharyngioma pathogenesis and outcome and also that the miRNA could modulate the Wnt signaling pathway in craniopharyngioma tumorigenesis.