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Three-dimensional Alginate-bead Culture of Human Pituitary Adenoma Cells
Published on: February 18, 2016
Next-generation sequencing of microRNAs reveals a unique expression pattern in different types of pituitary adenomas
Zongze He1, Longyi Chen1, Xiao Hu1
1Department of Neurosurgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
Abstract:
Pituitary adenomas (PAs) are considered the most common intracranial tumor to cause serious morbidity because of dysregulated pituitary hormone secretions. Aberrant expression of microRNAs (miRNAs) is correlated with the development and function of the pituitary gland as well as the tumorigenesis of hypothalamic-pituitary axis-related pituitary tumors. In this study, we showed the differential expression patterns of miRNAs in NFPAs (nonfunctioning pituitary adenomas), GHPAs (growth hormone-secreting pituitary adenomas) and PRLPAs (prolactin-secreting pituitary adenomas) compared to those in three normal pituitary glands using the HiSeq 2000 sequencing system (Illumina). We validated miRNA expression using real-time quantitative polymerase chain reaction (RT-qPCR) analyses of samples from 73 patients (13 GHPAs, 42 NFPAs, and 18 PRLPAs) and 6 normal pituitary gland. We observed that miR-34c-3p was significantly downregulated in our PRLPA samples (p < 0.01), along with miR-34b-5p, miR-378 and miR-338-5p (all p < 0.05). In NFPAs, miR-493-5p was downregulated, and miR-181b-5p was significantly upregulated (p < 0.01). In GHPAs, miR-184 was significantly upregulated (p < 0.05). We observed that the tumor suppressive miR-124-3p was downregulated in both NFPAs and GHPAs. Taken together, we showed distinctive miRNA expression patterns in these three PAs, and these miRNA signatures in PA may have therapeutic potential as novel biomarkers for each type of PA.
Insights
This study reveals distinct microRNA (miRNA) expression patterns in pituitary adenomas (PAs). These specific miRNA signatures could serve as potential biomarkers for nonfunctioning, growth hormone-secreting, and prolactin-secreting PAs.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Pituitary adenomas (PAs) are common intracranial tumors causing significant morbidity due to hormone dysregulation.
- Aberrant microRNA (miRNA) expression is linked to pituitary gland development, function, and tumorigenesis.
Purpose of the Study:
- To investigate differential miRNA expression patterns in nonfunctioning pituitary adenomas (NFPAs), growth hormone-secreting pituitary adenomas (GHPAs), and prolactin-secreting pituitary adenomas (PRLPAs).
- To identify potential miRNA biomarkers for specific PA subtypes.
Main Methods:
- High-throughput sequencing (HiSeq 2000) was used to profile miRNA expression in PA subtypes and normal pituitary glands.
- Real-time quantitative polymerase chain reaction (RT-qPCR) validated miRNA expression in 73 patient samples (13 GHPAs, 42 NFPAs, 18 PRLPAs) and 6 normal glands.
Main Results:
- Specific miRNAs were differentially expressed across PA subtypes: miR-34c-3p, miR-34b-5p, miR-378, and miR-338-5p were downregulated in PRLPAs.
- miR-493-5p was downregulated and miR-181b-5p upregulated in NFPAs.
- miR-184 was upregulated in GHPAs, while miR-124-3p was downregulated in both NFPAs and GHPAs.
Conclusions:
- Distinct miRNA expression profiles characterize NFPAs, GHPAs, and PRLPAs.
- These identified miRNA signatures hold potential as novel therapeutic targets and diagnostic biomarkers for pituitary adenomas.
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