Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease

Abstract

Polyamines (PA) are polycations with pleiotropic functions in cellular physiology and pathology. In particular, PA have been involved in the regulation of cell homeostasis and proliferation participating in the control of fundamental processes like DNA transcription, RNA translation, protein hypusination, autophagy and modulation of ion channels. Indeed, their dysregulation has been associated to inflammation, oxidative stress, neurodegeneration and cancer progression. Accordingly, PA intracellular levels, derived from the balance between uptake, biosynthesis, and catabolism, need to be tightly regulated. Among the mechanisms that fine-tune PA metabolic enzymes, emerging findings highlight the importance of noncoding RNAs (ncRNAs). Among the ncRNAs, microRNA, long noncoding RNA and circRNA are the most studied as regulators of gene expression and mRNA metabolism and their alteration have been frequently reported in pathological conditions, such as cancer progression and brain diseases. In this review, we will discuss the role of ncRNAs in the regulation of PA genes, with a particular emphasis on the changes of this modulation observed in health disorders.

Keywords: Gene expression; Noncoding RNA; Polyamine metabolism; Polyamines.

Fig. 1

Schematic diagram of polyamine metabolism. Biosynthetic and catabolic pathways are shown in green and in red respectively. Stars highlight the presence of a ncRNA regulation

Fig. 2

Schematic diagram of regulatory noncoding RNA classification. The key characteristics of each group are reported in the squared boxes

Fig. 3

Schematic diagram of circSMOX expression in muscle (left panel) and neuronal (right panel) cells. The conditions were circSMOX has been found upregulated are reported. Blue arrows indicate upregulation of expression