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Differential Expression of MicroRNAs in Silent and Functioning Corticotroph Tumors
Araceli García-Martínez1, Antonio C Fuentes-Fayos2,3,4,5, Carmen Fajardo6
1Research Laboratory, Alicante General University Hospital-Institute for Health and Biomedical Research (ISABIAL), CIBERER, 03010 Alicante, Spain.
Abstract:
The potential role of miRNAs in the silencing mechanisms of pituitary neuroendocrine tumors (PitNETs) has not been addressed. The aim of the present study was to evaluate the expression levels and the potential associated role of some miRNAs, pathways, and transcription factors in the silencing mechanisms of corticotroph tumors (CTs). Accordingly, the expression of miR-375, miR-383, miR-488, miR-200a and miR-103; of PKA, MAP3K8, MEK, MAPK3, NGFIB, NURR1, PITX1, and STAT3 were analyzed via qRT-PCR in 23 silent and 24 functioning CTs. miR-200a and miR-103 showed significantly higher expression in silent than in functioning CTs, even after eliminating the bias of tumor size, therefore enabling the differentiation between the two variants. Additionally, miR-383 correlated negatively with TBX19 in silent CTs, a transcription factor related with the processing of POMC that can participate in the silencing mechanisms of CTs. Finally, the gene expression levels of miR-488, miR-200a, and miR-103 were significantly higher in macroadenomas (functioning and silent) than in microadenomas. The evidence from this study indicates that miRNAs could be involved in the pathophysiology of CTs. The translational implications of these findings suggest that pharmacological treatments specifically targeting these miRNAs could become a promising therapeutic option for these patients.
Insights
MicroRNAs (miRNAs) show altered expression in silent pituitary neuroendocrine tumors (PitNETs). Specific miRNAs like miR-200a and miR-103 can differentiate tumor types, suggesting potential therapeutic targets.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Pituitary neuroendocrine tumors (PitNETs) encompass various subtypes, including corticotroph tumors (CTs).
- The specific mechanisms underlying the silencing of CTs remain poorly understood.
- MicroRNAs (miRNAs) are implicated in gene regulation and tumor development.
Purpose of the Study:
- To investigate the role of specific miRNAs in the silencing mechanisms of CTs.
- To analyze the expression levels of selected miRNAs, pathways, and transcription factors in functioning versus silent CTs.
- To explore the potential of miRNAs as biomarkers for CT classification.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of miR-375, miR-383, miR-488, miR-200a, miR-103, and associated genes.
- Tumor samples from 23 silent and 24 functioning CTs were analyzed.
- Statistical analysis was performed to correlate miRNA expression with tumor characteristics.
Main Results:
- miR-200a and miR-103 exhibited significantly higher expression in silent CTs compared to functioning CTs, irrespective of tumor size.
- miR-383 showed a negative correlation with the transcription factor TBX19 in silent CTs.
- Higher expression of miR-488, miR-200a, and miR-103 was observed in macroadenomas compared to microadenomas.
Conclusions:
- miRNAs are potentially involved in the pathophysiology of corticotroph tumors.
- Specific miRNAs can serve as differentiating markers between functioning and silent CTs.
- Targeting these miRNAs may offer novel therapeutic strategies for CT patients.
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