The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes.
BACKGROUND
Skin cancer is the most common cancer in the United States, and ultraviolet B (UVB) radiation-induced DNA damage is the major environmental factor underlying skin cancer development. p21, a p53-inducible protein, plays a key role in the cellular response to UVB-induced DNA damage.


METHODS
Through p21 silencing and overexpression, we investigated the role of p21 in apoptosis, proliferation, cell cycle arrest, and oxidative stress in UVB-irradiated HaCaT keratinocytes.


RESULTS
We found that UVB exposure induced significant p21 downregulation (p<0.05) and was associated with significantly increased apoptosis, significantly decreased proliferation, and significantly increased G2 phase arrest (p<0.05) in UVB-irradiated HaCaT keratinocytes. p21 silencing significantly promoted apoptosis, significantly inhibited G2 phase arrest, and significantly inhibited proliferation (p<0.05), but after UVB irradiation, p21 silencing demonstrated a less significant pro-apoptotic effect and a more significant inhibition of G2 phase arrest (p<0.05), which was reflected in significantly higher proliferative activity (p<0.05). p21 overexpression acted in an anti-apoptotic manner in the absence of UVB-induced DNA damage but acted in a pro-apoptotic manner in the presence of UVB-induced DNA damage, displaying an "antagonistic duality" similar to other growth-promoting oncoproteins. p53 expression mirrored p21 expression, suggesting a regulatory feedback mechanism between p21 and p53 expression. p21 overexpression significantly downregulated glutathione peroxidase and superoxide dismutase antioxidant activity (p<0.05) while significantly upregulating hydrogen peroxide and malondialdehyde content (p<0.05), suggesting a role in decreasing antioxidant defense capabilities in UVB-irradiated HaCaT keratinocytes.


CONCLUSIONS
These findings reveal that p21 may play a key role in HaCaT keratinocytes' response to UVB exposure.
Department of Dermatology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China (mainland).
Aijun
A
Chen
Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China (mainland).
Xin
X
Huang
Department of Dermatology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China (mainland).
Zhenan
Z
Xue
Department of Dermatology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China (mainland).
Di
D
Cao
Department of Dermatology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China (mainland).
Kun
K
Huang
Department of Dermatology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China (mainland).
Jin
J
Chen
Department of Dermatology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China (mainland).
Yun
Y
Pan
Department of Dermatology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China (mainland).
Yongliang
Y
Gao
D000704:Analysis of Variance; D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000528:radiation effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000528:radiation effects*; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D016159:Tumor Suppressor Protein p53; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase