Direct Interaction of miRNA and circRNA with the Oncosuppressor p53: An Intriguing Perspective in Cancer Research

SIMPLE SUMMARY: MicroRNAs and circular RNAs, which are single-stranded non-coding RNAs, play a key role as regulators at post-transcriptional level. Abnormal levels or dysregulation of miRNA or circRNA are linked to several cancerous pathologies. Starting from the evidence that some miRNAs and circRNAs are involved in the regulatory networks of the tumor suppressor protein p53, the possibility that a functional inhibition of p53 could arise from a direct interaction between p53 and oncogenic miRNAs or circRNAs was explored. Along this direction, the experimental evidence of the interaction between p53 and miRNAs and/or circRNAs is reviewed and discussed in connection with the development of new anticancer strategies. ABSTRACT: MicroRNAs (miRNAs) are linear single-stranded non-coding RNAs oligonucleotides, widely distributed in cells, playing a key role as regulators of gene expression at post-transcriptional level. Circular RNAs (circRNAs) are single-stranded RNA oligonucleotides forming a covalently closed continuous loop, which confers them a high structural stability and which may code for proteins or act as gene regulators. Abnormal levels or dysregulation of miRNA or circRNA are linked to several cancerous pathologies, so that they are receiving a large attention as diagnostic and prognostic tools. Some miRNAs and circRNAs are strongly involved in the regulatory networks of the transcription factor p53, which plays a pivotal role as tumor suppressor. Overexpression of miRNAs and/or circRNAs, as registered in a number of cancers, is associated to a concomitant inhibition of the p53 onco-suppressive function. Among other mechanisms, it was recently suggested that a functional inhibition of p53 could arise from a direct interaction between p53 and oncogenic miRNAs or circRNAs; a mechanism that might be reminiscent of the p53 inhibition by some E3 ubiquitin ligase such as MDM2 and COP1. Such evidence might deserve important implications for restoring the p53 anticancer functionality, and pave the way to intriguing perspectives for novel therapeutic strategies. In the present paper, the experimental evidence of the interaction between p53 and miRNAs and/or circRNAs is reviewed and discussed in connection with the development of new anticancer approaches.