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microRNA expression profile and differentially-expressed genes in prolactinomas following bromocriptine treatment
Chengde Wang1, Zhipeng Su, Nader Sanai
1Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, PR China.
Abstract:
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.
Insights
Bromocriptine treatment alters microRNA expression in prolactinomas, affecting tumor growth. Key microRNAs and genes like PDGFA and BMP4 are implicated in bromocriptine
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Prolactinomas are pituitary tumors often treated with bromocriptine.
- The role of microRNAs in bromocriptine-treated prolactinomas remains largely unknown.
- Understanding these molecular changes can optimize treatment strategies.
Purpose of the Study:
- To investigate microRNA expression profiles in prolactinomas before and after bromocriptine treatment.
- To identify specific microRNAs and associated genes involved in the response to bromocriptine therapy.
- To elucidate potential mechanisms of bromocriptine's pharmacotherapy in prolactinoma.
Main Methods:
- MicroRNA expression profiling using miRCURY LNA Array in six prolactinoma samples (treated vs. untreated).
- Validation of differentially expressed microRNAs via stem-loop real-time PCR.
- Gene Ontology (GO) and KEGG pathway analysis for functional annotation.
- Quantitative real-time PCR (qRT-PCR) to analyze related gene expression in 15 samples.
Main Results:
- Microarray analysis identified 80 upregulated and 71 downregulated microRNAs in bromocriptine-treated prolactinomas.
- miR-206, miR-516b, and miR-550 were significantly upregulated; miR-671-5p was downregulated post-treatment.
- Platelet-derived growth factor α polypeptide (PDGFA) was upregulated, while bone morphogenetic protein 4 (BMP4) was downregulated in treated samples.
Conclusions:
- Bromocriptine pharmacotherapy induces significant changes in microRNA expression in prolactinomas.
- Specific microRNAs likely play roles in modulating prolactinoma tumor growth under bromocriptine treatment.
- PDGFA and BMP4 are identified as potentially crucial genes in the mechanism of bromocriptine's action on prolactinoma.
