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Altered microRNA expression profile in human pituitary GH adenomas: down-regulation of miRNA targeting HMGA1, HMGA2,
Daniela D'Angelo1, Dario Palmieri, Paula Mussnich
1Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche (CNR) c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita` degli Studi di Napoli, Napoli, Italy.
Context:
MicroRNA (miRNA) are an important class of regulators of gene expression. Altered miRNA expression has been constantly found in human neoplasias and plays an important role in the process of carcinogenesis.
Objective:
The aim of this study was to identify specific miRNA whose expression is altered in GH-secreting pituitary adenomas.
Design:
Using a miRNACHIP microarray, we have analyzed the miRNA expression profile of human GH adenomas vs. normal pituitary gland.
Results:
We report the identification of a set of miRNA, including miR-34b, miR-326, miR-432, miR-548c-3p, miR-570, and miR-603, drastically and constantly down-regulated in GH adenomas. We demonstrate that these miRNA target genes such as high-mobility group A1 (HMGA1), HMGA2, and E2F1, whose overexpression and/or activation plays a critical role in pituitary tumorigenesis. We also show that the enforced expression of the down-regulated miRNA has a negative role on the growth regulation of pituitary adenoma cells. Finally, an inverse correlation is found between the expression of these miRNA and HMGA1 and HMGA2 protein levels in GH adenomas.
Conclusion:
Our study identifies a specific subset of miRNA, whose down-regulation might contribute to pituitary tumorigenesis.
Insights
This study identified specific microRNAs (miRNAs) that are down-regulated in growth hormone-secreting pituitary adenomas. Their reduced expression may contribute to pituitary tumor development by affecting key genes.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in various cancers.
- Altered miRNA expression is a hallmark of human neoplasias, including pituitary adenomas.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) with altered expression in growth hormone (GH)-secreting pituitary adenomas.
- To investigate the role of these miRNAs in the development of pituitary tumors.
Main Methods:
- Utilized miRNACHIP microarray to analyze miRNA expression profiles.
- Compared miRNA expression in human GH adenomas versus normal pituitary glands.
Main Results:
- Identified several down-regulated miRNAs (miR-34b, miR-326, miR-432, miR-548c-3p, miR-570, miR-603) in GH adenomas.
- Demonstrated that these miRNAs target genes like HMGA1, HMGA2, and E2F1, crucial for pituitary tumorigenesis.
- Showed that enforced miRNA expression inhibits pituitary adenoma cell growth and correlates inversely with HMGA1/HMGA2 protein levels.
Conclusions:
- A specific subset of down-regulated miRNAs may contribute to the development of pituitary adenomas.
- These findings highlight potential miRNA-based biomarkers or therapeutic targets for pituitary tumors.
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