MicroRNAs (miRNAs) are small, non-coding molecules that can suppress the expression of proteins by interfering with mRNA translation. We have investigated the role of microRNAs in the cell biology of human foreskin keratinocytes (HFKs). One intriguing example is microRNA-203 (miR-203) , a skin-specific microRNA which has been previously shown to negatively regulate p63 levels in HFKs, thereby influencing the ability of these cells to proliferate and/or differentiate. Since there is also evidence that p63 levels are related to p53 expression, we have investigated how the expression of p53 impacts upon miR-203 during proliferation and differentiation of HFKs. We demonstrate that miR-203 expression is reduced in HFKs where p53 function is compromised, either by knockout of p53 (p53i) or by the action of the viral oncoprotein E6. We show that the induction of miR-203 observed during calcium-induced differentiation of HFKs is significantly reduced in p53i HFKs and in HFKs expressing E6. We report that proliferation of HFKs is dependent on the level of miR-203 expression and that over-expression of miR-203 can help to reduce over-proliferation caused by the absence of p53. We also show that the induction of miR-203 in response to DNA damage is also reduced in the absence of p53. These results indicate that the expression of miR-203 is p53-dependent, thereby offering a mechanism which may explain the relationship between p53 and p63 during epidermal homeostasis, and potentially in the cellular response to DNA damage. In addition, we will also report on the involvement of other miRNAs which are highly expressed in the epithelium and which have important roles in keratinocyte biology and function.
|Title of host publication||Unknown Host Publication|
|Number of pages||200|
|Publication status||Accepted/In press - 5 Mar 2010|
|Event||IRISH ASSOCIATION FOR CANCER RESEARCH (IACR) ANNUAL MEETING 2010 - Galway, Ireland|
Duration: 5 Mar 2010 → …
|Conference||IRISH ASSOCIATION FOR CANCER RESEARCH (IACR) ANNUAL MEETING 2010|
|Period||5/03/10 → …|