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Differential microRNA Expression in USP8-Mutated and Wild-Type Corticotroph Pituitary Tumors Reflect the Difference

Mateusz Bujko1, Paulina Kober1, Joanna Boresowicz1

  • 1Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, Poland.

Journal of Clinical Medicine
|January 27, 2021
PubMed
Abstract

Insights

USP8 mutations in pituitary tumors alter microRNA profiles, reflecting disrupted ubiquitination. However, these microRNA changes do not directly explain gene expression differences between mutated and wild-type tumors.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Ubiquitin-specific protease 8 (USP8) mutations are common in pituitary tumors, affecting proteome and gene expression.
  • These mutations disrupt the ubiquitination process, a key cellular mechanism.
  • Understanding microRNA (miRNA) roles in USP8-mutated tumors is crucial.

Purpose of the Study:

  • To compare miRNA profiles in USP8-mutated versus wild-type corticotroph tumors.
  • To investigate the functional role of differential miRNA expression via integrated miRNA and mRNA analysis.

Main Methods:

  • Next-generation sequencing was used to analyze miRNA and gene expression.
  • Sanger sequencing identified USP8 mutations.
  • In silico prediction and correlation analysis identified miRNA targets.

Main Results:

  • 68 differentially expressed miRNAs were identified between USP8-mutated and wild-type tumors.
  • Enriched gene targets were primarily involved in protein ubiquitination.
  • Few miRNAs correlated with gene expression differences between tumor types.

Conclusions:

  • Differential miRNA expression in corticotropinomas reflects altered ubiquitination processes linked to USP8 status.
  • Observed miRNA expression changes do not directly account for gene expression differences between USP8-mutated and wild-type tumors.
Keywords:
Cushing’s diseaseUSP48USP8corticotroph PitNETgene expressionmiRNA expressionmutationnext generation sequencing

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