Introduction: Silencing mechanisms of corticotroph tumors (CT) remain unclear. Epigenetic mechanisms can occur during tumorigenesis. MiRNAs capable of inhibiting the expression of POMC have been described at the level of neurons of the hypothalamus, which gives us a basis to advance in the knowledge of CT.

Objectives: To determine if post-transcriptional regulation by miRNAs is involved in the silencing of CT.

Methods: We quantified the relative gene expression of 8 factors (PKA, MAP3K8, MEK, MAPK3, NGFIB, NURR1, PITX1, STAT3) and 5 miRNAs (miR375, miR383, miR488, miR200a, miR103) by qRT-PCR with TaqMan probes in 24 functioning CT (fCT) and 23 silent CT (sCT).

Results: miR200a and miR103 expression was higher in silent CT than in macro functioning CT (p = 0.049 and p = 0.05, respectively). Both miRNA biomarkers could be a good tool to distinguish between both variants (AUC = 0.739, 95%CI = 0.592-0.887, p = 0.007; AUC = 0.727, 95%CI = 0.574-0.880, p = 0.011, respectively). These two miRNAs correlated negatively with MAP3K8 (rho = -0.686, p = 0.001 and rho = -0.782, p < 0.001, respectively). MiR383 was up-regulated in functioning (3.607 ± 5.016) and silent (8.918 ± 12.009) CT compared with normal pituitary gland. Using different computational algorithms, we found that NEUROD1 was a potential target for miR383. Interestingly we observed a negative correlation between TBX19 and miR383 in both subtypes, stronger in silent CT (rho = -0.583, p = 0.007) than in functioning ones (rho = -0.431, p = 0.051). We also found other interesting potential targets for miR383, as SSTR2, SSTR3 and SSTR5. Finally, we observed a negative correlation between miR383 and the expression of STAT3 (rho = -0.544, p = 0.016) in silent CT.

Conclusions: MiR200a and miR103 may be involved in the silencing of this subtype and could be used as diagnostic tool. The negative correlation between miR383 and TBX19 expression could indicate a potential silencing mechanism of these tumors. Moreover, miR383 may be a possible therapeutic target in CT.