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

Pituitary. 2017 Aug;20(4):450-463. doi: 10.1007/s11102-017-0805-y.


Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ACTHoma; Crooke’s cell adenoma; MCM7; MiR-106b~25 cluster; MicroRNA; Pituitary adenoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Minichromosome Maintenance Complex Component 7 / genetics
  • Minichromosome Maintenance Complex Component 7 / metabolism*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Pituitary Neoplasms / genetics
  • Pituitary Neoplasms / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Young Adult


  • MicroRNAs
  • Minichromosome Maintenance Complex Component 7