Functional Genomics of PRUNE1 in Neurodevelopmental Disorders (NDDs) Tied to Medulloblastoma (MB) and Other Tumors.

Francesca Bibbò,Carmen Sorice,Massimo Zollo,Veronica Ferrucci

doi:10.3389/fonc.2021.758146

Abstract

We analyze the fundamental functions of Prune_1 in brain pathophysiology. We discuss the importance and maintenance of the function of Prune_1 and how its perturbation influences both brain pathological conditions, neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA; OMIM: 617481), and tumorigenesis of medulloblastoma (MB) with functional correlations to other tumors. A therapeutic view underlying recent discoveries identified small molecules and cell penetrating peptides to impair the interaction of Prune_1 with protein partners (e.g., Nm23-H1), thus further impairing intracellular and extracellular signaling (i.e., canonical Wnt and TGF-β pathways). Identifying the mechanism of action of Prune_1 as responsible for neurodevelopmental disorders (NDDs), we have recognized other genes which are found overexpressed in brain tumors (e.g., MB) with functional implications in neurodevelopmental processes, as mainly linked to changes in mitotic cell cycle processes. Thus, with Prune_1 being a significant target in NDDs, we discuss how its network of action can be dysregulated during brain development, thus generating cancer and metastatic dissemination.

Highlights

PRUNE_1, the human homolog of the Drosophila melanogaster pn gene, was firstly identified by viable mutations responsible for the brunish purple eye color compared to the red of wild-type fly (1)
Altogether, these findings suggest that AA7.1 is a nontoxic potential immunomodulatory molecule with the ability to modulate the inflammatory processes in the tumor microenvironment (TME), inhibiting the metastatic spread in Prune_1-overexpressing tumors
Brain tumorigenic cells can derive from neural progenitor cells (NPCs)

Summary

Introduction

PRUNE_1, the human homolog of the Drosophila melanogaster pn gene, was firstly identified by viable mutations responsible for the brunish purple eye color compared to the red of wild-type fly (1). Because of the enzymatic activities and its interaction with several proteins, Prune_1 was found able to modulate both intraand extracellular signaling cascades [including the canonical Wnt (8) and TGF-b (11) pathways] that regulate cell proliferation, motility, and epithelial–mesenchymal transition (EMT) processes.

Results

Conclusion