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microRNA expression profile and differentially-expressed genes in prolactinomas following bromocriptine treatment.

Oncology Reports

Adult, Antineoplastic Agents, therapeutic use, Bromocriptine, Cluster Analysis, Dopamine Agonists, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, drug effects, Gene Regulatory Networks, Humans, Male, MicroRNAs, genetics, Middle Aged, Pituitary Neoplasms, drug therapy, Prolactinoma, Young Adult

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      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 downregulated 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 α 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.

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