垂体泌乳素腺瘤组织中相关microRNA的表达

Differential expression analysis of prolactinoma-related microRNAs

目的 探讨垂体泌乳素（PRL）腺瘤组织中的microRNA（miRNA）表达与腺瘤形成、生长及激素分泌的关系.方法 利用Slexa测序技术分析miRNA在PRL腺瘤和正常垂体前叶组织中的差异表达,并用茎环引物（stem-loop） RT-PCR技术在27例PRL腺瘤和5例正常垂体前叶中加以验证.结果 通过Solexa测序对比PRL腺瘤与正常垂体前叶组织,发现39个丰度较高的miRNA存在差异性表达.进一步通过stem-loop RT-PCR验证,发现4个miRNA下调（miR-130a,miR-199b-3p,miR-200b,miR-125b,P＜0.05）;6个miRNA上调（miR-342-3p,miR-432,miR-23b,miR-493,miR-493＊,miR-664＊,P＜0.05）.其中miR-493＊,miR-432表达与泌乳素水平呈显著正相关（r=0.47,P＜0.05；r=0.528,P＜0.01）；miR-342-3p表达与肿瘤侵袭性呈正相关（r=0.402,P＜0.05）.结论 正常垂体前叶/PRL腺瘤、侵袭型/局限型PRL腺瘤、不同激素分泌水平PRL腺瘤之间存在着miRNA差异表达,提示miRNA可能参与垂体泌乳素腺瘤的成瘤、生长及激素分泌等生理过程.

Objective To explore the relationship between the prolactinoma-related microRNAs （miRNA） and the development,growth and hormone secretion of prolactinoma.Methods The technique of Solexa sequencing was employed to analyze the differential expressions of prolactinoma and normal anterior pituitary gland samples. And the stem-loop real-time polymerase chain reaction （PCR） was utilized for confirmation.Results According to the differentially expressed profiles of miRNAs,4 miRNAs were downregulated （miR-130a,miR-199b-3p,miR-200b,miR-125b,P〈0.05） and6 miRNAs up-regulated （miR-342-3p,miR-432,miR-23b,miR-493,miR-493 ＊,miR-664 ＊,P 〈 0.05）.The expression levels of miR-493 ＊ and miR-432 had a significant positive correlation with the serum level of prolactin （ r =0.47,P 〈0.05 ; r =0.528,P 〈 0.01 ） while miR-342-3p a significantly positive correlation with the invasiveness （ r =0.402,P 〈 0.05 ）.Conclusion miRNAs are differentially expressed between normal anterior pituitary gland and prolactinomas,between invasive and localized prolactinomas and among different hormone secretion levels. It suggests that miRNAs may be involved in the physiological process of development,growth and hormone secretion of prolactinoma.