Abstract
Simple SummaryMicroRNAs are small non-coding RNAs, acting as post-transcriptional regulators of gene expression. In the last two decades, their role in cancer as oncogenes (oncomir), as well as tumor suppressors, has been extensively demonstrated. Recently, epitranscriptomics, namely the study of RNA modifications, has emerged as a new field of great interest, being an additional layer in the regulation of gene expression. Almost all classes of eukaryotic RNAs, including miRNAs, undergo epitranscriptomic modifications. Alterations of RNA modification pathways have been described for many diseases—in particular, in the context of malignancies. Here, we reviewed the current knowledge on the potential link between epitranscriptomic modifications of miRNAs and cancer.MicroRNAs are pervasive regulators of gene expression at the post-transcriptional level in metazoan, playing key roles in several physiological and pathological processes. Accordingly, these small non-coding RNAs are also involved in cancer development and progression. Furthermore, miRNAs represent valuable diagnostic and prognostic biomarkers in malignancies. In the last twenty years, the role of RNA modifications in fine-tuning gene expressions at several levels has been unraveled. All RNA species may undergo post-transcriptional modifications, collectively referred to as epitranscriptomic modifications, which, in many instances, affect RNA molecule properties. miRNAs are not an exception, in this respect, and they have been shown to undergo several post-transcriptional modifications. In this review, we will summarize the recent findings concerning miRNA epitranscriptomic modifications, focusing on their potential role in cancer development and progression.
Highlights
MicroRNAs are a class of short, non-coding RNAs that control gene expression at the post-transcriptional level via either translational repression or mRNA degradation.Since miRNAs act as pervasive regulators of gene expression, it is not surprising that they were involved in normal animal development and in a variety of biological processes [1,2]
A-to-I editing is catalyzed by enzymes highly conserved in vertebrates, called Adenosine Deaminases Acting on RNA (ADAR) [92]
Our understanding of the mechanisms underlying the epitranscriptomic regulation of miRNAs is still potentially biased by the relatively small number of modifications which have been widely investigated in miRNAs, with most reports focused on m6A and A-to-I editing
Summary
MicroRNAs (miRNAs) are a class of short, non-coding RNAs that control gene expression at the post-transcriptional level via either translational repression or mRNA degradation. Several RNA modifications directly affect the RNA structure and/or base pairing, requiring no “reader” proteins to exert their functions. Mature miRNAs interact with the RNA-binding proteins belonging to the Argonaute family (AGO), becoming integral components of the RNA-Induced Silencing Complex (RISC) (reviewed in references [46,47]). The authors identified NOP2/Sun RNA Methyltransferase 2 (Nsun2), a well-characterized m5C “writer” [21,77], as the “writer” enzyme of this modification Their data suggested that a m6A modification may prevent pri-miR-125b-2 processing into mature miR-125b [76]. Konno and colleagues [91] showed that the m6A modification of let-7a-5p and miR-17-5p caused a large structural change in the RISC complex, which affected the target RNA recognition. In pancreatic and CRC tissues, the m6A levels on let-7a-5p and miR-17-5p increased without affecting the miRNA expression level
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