Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke’s cell morphology

• DOI: 10.1007/s11102-017-0805-y
• Publication Date: 2017-04-21T11:33:51Z
• Authors: Filip Garbicz; Dawid Mehlich; Beata Rak; Emir Sajjad; Maria Maksymowicz; Wiktor Paskal; Grzegorz Zieliński; Paweł K. Włodarski
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Adolescent; Middle Aged; Minichromosome Maintenance Complex Component 7; Real-Time Polymerase Chain Reaction; Article; MicroRNAs; Young Adult; 03 medical and health sciences; Humans; Female; Pituitary Neoplasms; Neoplasm Recurrence, Local; Aged

MCM7 (minichromosome maintenance complex component 7), a DNA replication licensing factor, is a host gene for the oncogenic miR-106b~25 cluster. It has been recently revealed as a relevant prognostic biomarker in a variety of cancers, including pituitary adenomas. The purpose of this study was to assess whether miR-106b~25 and MCM7 levels correlate with tumor invasiveness in a cohort of ACTH-immunopositive adenomas.Tissue samples were obtained intraoperatively from 25 patients with pituitary adenoma. Tumor invasiveness was assessed according to the Knosp grading scale. MCM7, Ki-67 and TP53 levels were assessed by immunohistochemical staining, while the expression of miR-106b-5p, miR-93-5p, miR-93-3p and miR-25-3p were measured using quantitative real-time PCR performed on RNA isolated from FFPE tissues.We have found a significant increase in MCM7 and Ki-67 labeling indices in invasive ACTHomas. Moreover, MCM7 was ubiquitously overexpressed in Crooke's cell adenomas. The expression of miR-93-5p was significantly elevated in invasive compared to noninvasive tumors. In addition, all four microRNAs from the miR-106b~25 cluster displayed marked upregulation in Crooke's cell adenomas. Remarkably, MCM7 and miR-106b-5p both strongly correlated with Knosp grade. A combination of MCM7 LI and miR-106b~25 cluster expression was able to accurately differentiate invasive from noninvasive tumors and had a significant discriminatory ability to predict postoperative tumor recurrence/progression.miR-106b~25 and its host gene MCM7 are potential novel biomarkers for invasive ACTH-immunopositive pituitary adenomas. Additionally, they are both significantly upregulated in rare Crooke's cell adenomas and might therefore contribute to their aggressive phenotype.