Proteomic and Transcriptomic Analysis Identify Spliceosome as a Significant Component of the Molecular Machinery in the Pituitary Tumors Derived from POU1F1- and NR5A1-Cell Lineages.

Keiko Taniguchi‐Ponciano ,Sophia Mercado-Medrez,Ernesto Sosa,Gloria Silva-Román,Eduardo Peña-Martínez,Gerardo Guinto,Baldomero Gonzales-Virla,Sandra Vela-Patiño,Ana Laura Espinosa-De-Los-Monteros,Etual Espinosa-Cárdenas ,Daniel Marrero‐Rodríguez ,Blas López-Félix ,Guadalupe Vargas‐Ortega ,Aldo Ferreira‐Hermosillo ,Héctor Quezada ,Ana Laura Guzmán-Ortiz ,Erick Gómez‐Apo ,Claudia Ramírez‐Rentería ,Laura Chávez-Macías ,Moisés Mercado

doi:10.3390/genes11121422

Abstract

Background: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. Methods: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. Results: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. Conclusions: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.

Highlights

Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes
Females predominated among patients harboring POU1F1-derived hormone secreting tumors (POU1F1), whereas there were no differences in gender in the NR5A1-derived clinically non-functioning PA
While 81.8% of the POU1F1-derived functioning adenomas were found to be recurrent upon follow up, that was the case for only 50% of the NR5A1-derived non-functioning pituitary adenomas (NFPA)

Summary

Introduction

Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out. Pituitary adenomas (PA) account for 10–25% of the total intracranial tumors, and despite their very low malignancy rate they cause significant morbidity [1]. Pituitary tumors are classified immunohistochemically according to their hormone profile and transcription factor expression. Splicing of mRNA precursors is required for the maturation of almost all human mRNA’s and is a key step in the regulation of the expression of many genes [4]. Alternative splicing is a ubiquitous regulatory mechanism of gene expression that allows generation of more than one unique mRNA species from a single gene resulting in the synthesis of different protein isoforms.

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Results

Conclusion