Hou Lichao, Bowman Linda, Meighan Terence G, Pratheeshkumar Poyil, Shi Xianglin, Ding Min
Graduate Center for Toxicology, College of Medicine, The University of Kentucky, Lexington, KY 40503, USA; Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA; Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, PR China.
Exp Toxicol Pathol. 2013 Nov;65(7-8):1145-8. doi: 10.1016/j.etp.2013.05.006. Epub 2013 Jul 26.
Ultraviolet (UV) irradiation plays a major role in the development of human skin cancer. The present study examined the alterations of miR-21-PDCD4 signaling in a mouse epidermal cell line (JB6 P(+)) post exposure to UVB irradiation. The results showed that (1) UVB caused PDCD4 inhibition in JB6 cells; (2) exposure of cells to UVB caused a significant increase of miR-21, the upstream regulator of PDCD4, expression; (3) both inhibition of ERKs with U0126 and inhibition of p38 with SB203580 significantly reversed UVB-induced PDCD4 inhibition; (4) ROS scavenger, N-acetyl-l-cysteine reversed the inhibitory effect of UVB on PDCD4 expression. The above results suggested that UVB induced PDCD4 inhibition, which may be mediated through ROS, especially endogenous H2O2 and p38 and ERKs phosphorylation. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of UVB-induced carcinogenesis.
紫外线（UV）照射在人类皮肤癌的发生发展中起主要作用。本研究检测了小鼠表皮细胞系（JB6 P(+)）在暴露于UVB照射后miR-21-PDCD4信号通路的变化。结果表明：（1）UVB导致JB6细胞中PDCD4受到抑制；（2）细胞暴露于UVB后，PDCD4的上游调节因子miR-21的表达显著增加；（3）用U0126抑制ERK和用SB203580抑制p38均能显著逆转UVB诱导的PDCD4抑制；（4）活性氧清除剂N-乙酰-L-半胱氨酸可逆转UVB对PDCD4表达的抑制作用。上述结果表明，UVB诱导的PDCD4抑制可能通过活性氧介导，尤其是内源性H2O2以及p38和ERK的磷酸化。阐明与这些事件相关的复杂机制可能为深入了解UVB诱导的致癌作用的起始和进展提供思路。
