无功能垂体腺瘤与正常垂体中microRNAs的差异表达

Differential Expression of MicroRNAs in Nonfunctioning Pituitary Adenoma and Normal Pituitary

【目的】检测微小分子RNA(microRNA,miRNA)在无功能垂体腺瘤(NFA)和正常垂体(NP)组织中的差异表达,探讨微小分子RNA在垂体腺瘤发生发展过程中的作用。【方法】收集6例NFA和6例NP,应用miRCURYTM LNA基因芯片技术分析差异表达的miRNA,并应用荧光定量PCR对部分差异表达的miRNA进行验证。【结果】与正常标本相比,肿瘤标本中miR-124、-141、-200c、-223、-297、-299-5p、-32、-340、-378、-491-3p、-519d、-525-5p、-550、-551a、-574-5p、-583、-662、-768-3p、-885-5p、-890等20个miRNAs显著上调(上调到>2.0倍),miR-125b-1、-132、-17、-192、-193a-3p、-193a-5p、-21、-302c、-30b、-31、-376b、-490-5p、-542-3p、-567、-622、-637、-654-3p、-658等18个miRNAs明显下调(下调到0.5倍以下)。一些差异表达的miRNA参与细胞的增殖和凋亡过程,提示它们的变化可能与垂体腺瘤的发生发展有关。【结论】miRNAs表达的变化可能参与无功能垂体腺瘤的发生,而miRNAs靶基因的确立可以为无功能垂体腺瘤的发生机制提供新的理论依据。

【Objective】 The purpose of this study was to identify different expression of miRNAs between nonfunctioning pituitary adenoma（NFP） and normal pituitary（NP）,and investigate the role of miRNA in development and progression of pituitary adenomas.【Methods】 Six NFA and 6 NP were collected.The miRNAs in NFA and NP were analyzed by miRCURYTM LNA array and some differentially expressed miRNAs were confirmed by quantitative real-time PCR.【Results】 Compared with NP,20 microRNAs were significantly increased（fold change to more than 2.0） ： miR-124,-141,-200c,-223,-297,-299-5p,-32,-340,-378,-491-3p,-519d,-525-5p,-550,-551a,-574-5p,-583,-662,-768-3p,-885-5p,and-890;Eighteen microRNAs including miR-125b-1,-132,-17,-192,-193a-3p,-193a-5p,-21,-302c,-30b,-31,-376b,-490-5p,-542-3p,-567,-622,-637,-654-3p,and-658 decreased significantly（fold change to less than 0.5） in NFAs.Several miRNAs identified in our study are involved in cell proliferation and apoptosis indicated their changes are associated with tumor development and progression.【Conclusion】 Our results demonstrated that altered miRNAs expression may be involved in NFAs transformation and the establishment of target genes of miRNAs may elucidate molecular mechanisms involved in the pathogenesis of pituitary adenomas.