miR-34a-5p and miR-34a-3p contribute to the signaling pathway of p53 by targeting overlapping sets of genes

TL;DR

This study re-examines the roles of miR-34a-5p and miR-34a-3p in p53 signaling, revealing they target overlapping genes and form a novel regulatory loop that enhances p53 response to stress.

Contribution

It demonstrates that both strands of miR-34a are functionally active and identifies a new incoherent feed-forward loop involving p53, MDM2, and miR-34a.

Findings

miR-34a-5p and miR-34a-3p target overlapping genes

THBS1 is involved in cancer and metastasis processes

p53, MDM2, and miR-34a form a novel regulatory loop

Abstract

In contrary to the common belief that only one strand of the pre-miRNA is active (usually the 5p one that is the more abundant) while the second one (miRNA*) is discarded, functional 5p and 3p have been observed for many miRNAs. Among those miRNAs is miR-34a which is a target gene of the tumor suppressor p53. In this paper we have re-examined the role of miR-34a-5p and miR-34a-3p in the signaling pathway of p53. We found that they target overlapping sets of genes (MDM2 and THBS1). By a GO enrichment analysis we found that THBS1 is involved in cancer and metastasis relevant processes. We have also deduce that p53, MDM2 and miR-34a are linked by a type 1 incoherent FFL that represent a novel mechanism for accelerating the response of p53 to external stress signals.