microRNA expression profile and differentially-expressed genes in prolactinomas following bromocriptine treatment
microRNA expression profile and differentially-expressed genes in prolactinomas following bromocriptine treatment
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DOI：
10.3892/or.2012.1690
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发表时间：
2012-05-01
期刊：
影响因子：
4.2
通讯作者：
Wu, Zhe Bao
中科院分区：
文献类型：
--
作者：
Wang, Chengde;Su, Zhipeng;Wu, Zhe Bao
关于溴隐亭治疗泌乳素瘤中microRNA的功能知之甚少。该研究的目的是探索与溴隐亭治疗的泌乳素瘤相关的microRNA。根据显微手术前是否接受溴隐亭治疗选择6例泌乳素瘤样本，并通过miRCURY LNA Array筛选溴隐亭治疗和未治疗泌乳素瘤的microRNA表达谱。采用茎环实时荧光定量PCR技术对芯片中差异表达的microRNA进行验证，并进行基因本体分析和KEGG通路分析。另外，采用qRT-PCR方法对15例泌乳素腺瘤中microRNA的相关基因进行分析。通过微阵列进行的初步分析产生了一个列表，与未治疗的泌乳素瘤相比，治疗的泌乳素瘤中有80种上调的microRNA和71种下调的microRNA。通过qRT-PCR证实miR-206、miR-516 b和miR-550在治疗的泌乳素瘤中显著上调，而miR-671- 5 p在治疗的泌乳素瘤中显著下调。结合GO和KEGG通路注释的microRNA-mRNA网络分析显示了一些关键因素。血小板源性生长因子a多肽（PDGFA）和骨形态发生蛋白4（BMP 4）在两组间有差异表达。PDGFA在治疗的泌乳素瘤中显著上调，而BMP 4在治疗的泌乳素瘤中显著下调。我们的研究揭示了药物治疗后泌乳素瘤中microRNAs的差异表达。特异性microRNA可能参与溴隐亭药物治疗对泌乳素瘤生长的抑制或促进作用。PDGFA和BMP 4可能参与了泌乳素瘤的药物治疗机制。
Little is known about the function of microRNAs in prolactinomas treated with bromocriptine. The aim of the study was to explore the microRNAs associated with bromocriptine-treated prolactinomas. Six prolactinoma samples were selected according to whether they received bromocriptine treatment or not before microsurgery, and microRNA expression profiles of bromocriptine-treated and untreated prolactinomas were screened by the miRCURY LNA Array. The differentially expressed microRNAs in microarrays were further validated by stem-loop real-time PCR and subjected to gene ontology analysis and KEGG pathway analysis. In addition, related genes of microRNAs were analyzed by qRT-PCR in 15 prolactinoma samples. The initial analysis by microarrays generated a list of 80 upregulated microRNAs and 71 down regulated microRNAs in treated prolactinomas compared to untreated prolactinomas. miR-206, miR-516b and miR-550 were confirmed to be significantly upregulated, while miR-671-5p was confirmed to be significantly downregulated in treated prolactinomas by qRT-PCR. microRNA-mRNA network analysis integrating GO and KEGG pathway annotation displayed some critical factors. Platelet-derived growth factor a polypeptide (PDGFA) and bone morphogenetic protein 4 (BMP4), were verified to be differentially expressed between the two groups. PDGFA was significantly upregulated in treated prolactinomas, while BMP4 was significantly downregulated in treated prolactinomas. Our study reveals differential expression of microRNAs in prolactinoma after pharmacotherapy. Specific microRNAs may be involved in the inhibition or promotion of prolactinoma tumor growth impacted by bromocriptine pharmacotherapy. PDGFA and BMP4 may be involved in the pharmacotherapy mechanism of prolactinoma.