Abstract
Tumour progression is accompanied by rapid cell proliferation, loss of differentiation, the reprogramming of energy metabolism, loss of adhesion, escape of immune surveillance, induction of angiogenesis, and metastasis. Both coding and regulatory RNAs expressed by tumour cells and circulating in the blood are involved in all stages of tumour progression. Among the important tumour-associated RNAs are intracellular coding RNAs that determine the routes of metabolic pathways, cell cycle control, angiogenesis, adhesion, apoptosis and pathways responsible for transformation, and intracellular and extracellular non-coding RNAs involved in regulation of the expression of their proto-oncogenic and oncosuppressing mRNAs. Considering the diversity/variability of biological functions of RNAs, it becomes evident that extracellular RNAs represent important regulators of cell-to-cell communication and intracellular cascades that maintain cell proliferation and differentiation. In connection with the elucidation of such an important role for RNA, a surge in interest in RNA-degrading enzymes has increased. Natural ribonucleases (RNases) participate in various cellular processes including miRNA biogenesis, RNA decay and degradation that has determined their principal role in the sustention of RNA homeostasis in cells. Findings were obtained on the contribution of some endogenous ribonucleases in the maintenance of normal cell RNA homeostasis, which thus prevents cell transformation. These findings directed attention to exogenous ribonucleases as tools to compensate for the malfunction of endogenous ones. Recently a number of proteins with ribonuclease activity were discovered whose intracellular function remains unknown. Thus, the comprehensive investigation of physiological roles of RNases is still required. In this review we focused on the control mechanisms of cell transformation by endogenous ribonucleases, and the possibility of replacing malfunctioning enzymes with exogenous ones.
Highlights
In this review we focused on the control mechanisms of cell transformation by endogenous ribonucleases, and the possibility of replacing malfunctioning enzymes with exogenous ones
It has been suggested that changes in intracellular tumourassociated RNA levels observed after treatment with exogenous RNases may be the result of both direct degradation of messenger RNA (mRNA) and miRNAs that suppress the expression of certain genes, and/ or generation of new siRNA-like molecules that can participate in the regulation of intracellular processes by the mechanism of RNA interference (Zhao et al, 2008; Saxena et al, 2009)
Named “house-keeping” endogenous ribonucleases are involved in the control of RNA homeostasis and the discarding of aberrant RNAs providing the proper functioning of RNA orchestra in the cell
Summary
Among the extracellular miRNA (ex-miRNA), mRNA fragments encoding tumour-associated antigens were detected, i.e. proteins that are expressed at low level in the cell, but overexpressed upon tumour progression. Many factors participated in regulation of gene expression at the mRNA level These factors are non-coding RNAs, RNA-binding proteins and RNases that maintain RNA-homeostasis in cells and discard aberrant RNAs through the degradation and turnover of transcripts, control of RNA decay, and biogenesis of miRNAs. Disruption of mentioned processes is mainly associated with distortion of expression or the improper functioning of these factors followed by cell transformation and tumour development. Disruption of mentioned processes is mainly associated with distortion of expression or the improper functioning of these factors followed by cell transformation and tumour development Among these factors, RNases play quite important role since they regulate the turnover of various transcripts at every stage of the cell cycle and participate in the processing of RNA involved in translation control. Nowadays a lot of information has appeared expanding the supervisory function of exogenous ribonucleases in the RNA world (Tables 1 and 3) and their intracellular RNA-targets (Figure 1)
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