Abstract
Simple SummaryThe dysregulation of RNA interference (RNAi) has often been observed in cancers, where the main focus of research has been on the small RNA molecules directing RNAi. In this review, we focus on the activity of Argonaute proteins, central components of RNAi, in tumorigenesis, and also highlight their potential applications in grading tumors and anti-cancer therapies.Argonaute proteins (AGOs) play crucial roles in RNA-induced silencing complex (RISC) formation and activity. AGOs loaded with small RNA molecules (miRNA or siRNA) either catalyze endoribonucleolytic cleavage of target RNAs or recruit factors responsible for translational silencing and target destabilization. miRNAs are well characterized and broadly studied in tumorigenesis; nevertheless, the functions of the AGOs in cancers have lagged behind. Here, we discuss the current state of knowledge on the role of AGOs in tumorigenesis, highlighting canonical and non-canonical functions of AGOs in cancer cells, as well as the biomarker potential of AGO expression in different of tumor types. Furthermore, we point to the possible application of the AGOs in development of novel therapeutic approaches.
Highlights
RNA interference (RNAi) plays a crucial role in post-transcriptional regulation of gene expression
AGO2 infactor, 76 colorectal tumor samples revealed a significant found to be an adverseofprognosis in this case for breast cancer
Even minute dysregulations of miRNA molecules and proteins engaged in RNAi may constitute the basis of severe malignancies, including cancer
Summary
RNA interference (RNAi) plays a crucial role in post-transcriptional regulation of gene expression. RNAi is mediated by three classes of small RNA (smRNA), approximately 20–25 nt long, endogenous piwiRNA (piRNA), microRNAs (miRNAs) or artificial small interfering RNAs (siRNAs). These smRNAs are loaded to a member of the Argonaute (AGO) protein family, which comprises an AGO subclass (loaded with si/miRNA) and PIWI subclass (loaded with piRNA) [1]. The smRNA profiles greatly differ spatiotemporally, which is characteristic for each cellular lineage throughout maturation [5] In such a manner, AGO1–4 protein expression is tightly controlled during development. The 2010s brought a substantial number of reports documenting AGO protein function, dysregulated expression, and mutations in cancer cells and tissues (Figure 1c). We provide a scrutinized summary of the relationship between AGO1–4 proteins and tumorigenesis
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