title: MicroRNAs and p63 in epithelial stemness.
abstract: MicroRNAs (miRs) are a class of small noncoding RNAs that suppress the expression of protein-coding genes by repressing protein translation. Although the roles that miRs and the miR processing machinery have in regulating epithelial stem cell biology are not fully understood, their fundamental contributions to these processes have been demonstrated over the last few years. The p53-family member p63 is an essential transcription factor for epidermal morphogenesis and homeostasis. p63 functions as a determinant for keratinocyte cell fate and helps to regulate the balance between stemness, differentiation and senescence. An important factor that regulates p63 function is the reciprocal interaction between p63 and miRs. Some miRs control p63 expression, and p63 regulates the miR expression profile in the epidermis. p63 controls miR expression at different levels. It directly regulates the transcription of several miRs and indirectly regulates their processing by regulating the expression of the miR processing components Dicer and DGCR8. In this review, we will discuss the recent findings on the miR-p63 interaction in epidermal biology, particularly focusing on the ΔNp63-dependent regulation of DGCR8 recently described in the ΔNp63(-/-) mouse. We provide a unified view of the current knowledge and discuss the apparent discrepancies and perspective therapeutic opportunities.
authors.affiliation: 1] Biochemistry Laboratory, IDI-IRCCS, Rome 00133, Italy [2] Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome 00133, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Candi
authors.affiliation: Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK.
authors.forename: I
authors.initials: I
authors.lastname: Amelio
authors.affiliation: Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK.
authors.forename: M
authors.initials: M
authors.lastname: Agostini
authors.affiliation: 1] Biochemistry Laboratory, IDI-IRCCS, Rome 00133, Italy [2] Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome 00133, Italy [3] Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK.
authors.forename: G
authors.initials: G
authors.lastname: Melino
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C474043:DGCR8 protein, human; C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins; D043244:Ribonuclease III