Immunofluorescence-based screening identifies germ cell associated microRNA 302 as an antagonist to p63 expression

The tumor suppressor homologue p63 is required for proper skin and limb development, but specific isoforms of it also act as a "guardian of the germline." To gain insight into the regulation of p63 expression, we performed immunofluorescence-based screening assays. Using a large collection of microRNA expression plasmids, we identified microRNAs of the 302 cluster as potent suppressors of p63 accumulation in various cell species. MiR-302 reduces p63 protein and mRNA levels through two target sites within the p63 3' untranslated region. In testicular cancer cells, endogenous miR-302 contributes to the suppression of p63. MiR-302 might also contribute to the elimination of p63 in mature oocytes. Thus, miR-302 appears as part of a stringent regulatory mechanism for p63 in germ cells, reminiscent of the tight control for p53 levels in somatic cells.