The expression of miR-124 increases in aged skin to cause cell senescence and it decreases in squamous cell carcinoma.
Skin senescence is induced by various factors including intrinsic aging and extrinsic aging. The current study compared the expression of microRNAs in young facial skin and senescent facial skin, and this study identified skin aging-related microRNAs. According to the results from a microRNA PCR Array, miR-124 was the microRNA that increased the most in senescent skin compared to young skin. Real-time PCR with a greater number of samples indicated that the increase in miR-124 levels in senescent facial skin was statistically significant. In situ hybridization was performed, and results indicated that the signal for miR-124 was evident in keratinocytes of senescent skin but not in those of young skin. The morphology of cultured normal human epidermal keratinocytes (NHEKs) transfected with a miR-124 mimic changed to an enlarged and irregular shape. In addition, the number of NHEKs positive for senescence-associated β-galactosidase (SA-β-gal) increased significantly as a result of the overexpression of the miR-124 mimic. The expression of miR-124 increased in UVB-irradiated NHEKs compared to controls in a dose-dependent manner. Expression of miR-124 in A431, a human cutaneous squamous cell carcinoma (SCC) cell line, decreased significantly compared to that in NHEKs. Forced overexpression of miR-124 as a result of the transfection of a miR-124 mimic in A431 resulted in the significant suppression of the proportion of cancer cells. The current results indicated that miR-124 increases as a result of cell senescence and that it decreases during tumorigenesis. The effect of supplementation of miR-124 in an SCC cell line suggests that senescence induction therapy with microRNA may be a new therapeutic approach for treatment of SCC.
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University.
Miho
M
Harada
Masatoshi
M
Jinnin
Zhongzhi
Z
Wang
Ayaka
A
Hirano
Yukiko
Y
Tomizawa
Tomomi
T
Kira
Toshikatsu
T
Igata
Shinichi
S
Masuguchi
Satoshi
S
Fukushima
Hironobu
H
Ihn
D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
C509207:MIRN124 microRNA, human; D035683:MicroRNAs