MicroRNA involvement in keratinocyte proliferation and differentiation

Declan McKenna, Simon McDade, Daksha Patel, Dennis McCance

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

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.
LanguageEnglish
Title of host publicationUnknown Host Publication
Number of pages200
Publication statusAccepted/In press - 5 Mar 2010
EventIRISH ASSOCIATION FOR CANCER RESEARCH (IACR) ANNUAL MEETING 2010 - Galway, Ireland
Duration: 5 Mar 2010 → …

Conference

ConferenceIRISH ASSOCIATION FOR CANCER RESEARCH (IACR) ANNUAL MEETING 2010
Period5/03/10 → …

Fingerprint

MicroRNAs
Keratinocytes
Foreskin
DNA Damage
Oncogene Proteins
Protein Biosynthesis
Cell Biology
Homeostasis
Epithelium
Calcium
Skin

Keywords

  • microRNA
  • miR-203
  • keratinocyte
  • p53
  • p63

Cite this

McKenna, D., McDade, S., Patel, D., & McCance, D. (Accepted/In press). MicroRNA involvement in keratinocyte proliferation and differentiation. In Unknown Host Publication
McKenna, Declan ; McDade, Simon ; Patel, Daksha ; McCance, Dennis. / MicroRNA involvement in keratinocyte proliferation and differentiation. Unknown Host Publication. 2010.
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McKenna, D, McDade, S, Patel, D & McCance, D 2010, MicroRNA involvement in keratinocyte proliferation and differentiation. in Unknown Host Publication. IRISH ASSOCIATION FOR CANCER RESEARCH (IACR) ANNUAL MEETING 2010, 5/03/10.

MicroRNA involvement in keratinocyte proliferation and differentiation. / McKenna, Declan; McDade, Simon; Patel, Daksha; McCance, Dennis.

Unknown Host Publication. 2010.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

TY - GEN

T1 - MicroRNA involvement in keratinocyte proliferation and differentiation

AU - McKenna, Declan

AU - McDade, Simon

AU - Patel, Daksha

AU - McCance, Dennis

PY - 2010/3/5

Y1 - 2010/3/5

N2 - 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.

AB - 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.

KW - microRNA

KW - miR-203

KW - keratinocyte

KW - p53

KW - p63

M3 - Conference contribution

BT - Unknown Host Publication

ER -

McKenna D, McDade S, Patel D, McCance D. MicroRNA involvement in keratinocyte proliferation and differentiation. In Unknown Host Publication. 2010