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. 2020 Jun 12;9(6):1838.
doi: 10.3390/jcm9061838.

Differential Expression of MicroRNAs in Silent and Functioning Corticotroph Tumors

Araceli García-Martínez  1 , Antonio C Fuentes-Fayos  2   3   4   5 , Carmen Fajardo  6 , Cristina Lamas  7 , Rosa Cámara  8 , Beatriz López-Muñoz  9 , Ignacio Aranda  10 , Raúl M Luque  2   3   4   5 , Antonio Picó  11
Affiliations

Differential Expression of MicroRNAs in Silent and Functioning Corticotroph Tumors

Araceli García-Martínez et al. J Clin Med. .

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.

Keywords: corticotroph tumors; miRNA; pituitary neuroendocrine tumors; transcriptional regulation.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Gene expression differences (fold change) of miR-200a, miR-103, miR-488, miR-375 and miR-383 between silent CTs (corticotroph tumors) and functioning CTs. * p < 0.05; ** p < 0.01.
Figure 2
Figure 2
HeatMap between gene and pathways involved in the silencing of corticotroph tumors. (a) Functioning corticotroph tumors (n = 24); (b) Silent corticotroph tumors (n = 23). Legend of numbers associated with colors refers to the coefficients of correlation.
Figure 3
Figure 3
Correlations among TBX19, NEUROD1 and miR-383. According to this scheme, miR-383 could negatively modulate the expression of the transcription factor of the corticotroph lineage, Tpit, through the direct inhibition of TBX19 mRNA and by the indirect stimulation of NEUROD1 mRNA.
Figure 4
Figure 4
(a) Gene expression differences (fold change) of miR-488, miR-200a, miR-103, miR-375, and miR-383 between macro and micro corticotroph tumors; (b) gene expression differences of miR-488 and miR-200a between invasive and non-invasive corticotroph tumors. * p < 0.05; ** p < 0.01.
See this image and copyright information in PMC

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