Abstract
Ultraviolet (UV) irradiation from the sunlight is a major etiologic factor for premature skin aging. Long noncoding RNAs (lncRNAs) are involved in various biological processes, and their roles in UV irradiation-induced skin aging have recently been described. Previously, we found that the lncRNA RP11-670E13.6 was up-regulated and delayed cellular senescence in UVB-irradiated primary human dermal fibroblasts. Here, we performed further investigations of RP11-670E13.6 function. The results showed that this lncRNA directly bound to miR-663a and functioned as a sponge for miR-663a to modulate the derepression of Cdk4 and Cdk6, thereby delaying cellular senescence during UV irradiation-induced skin photoaging. Moreover, we found that RP11-670E13.6 may facilitate DNA damage repair by increasing ATM and γH2A.X levels. In addition, heterogeneous nuclear ribonucleoprotein H physically interacted with RP11-670E13.6 and blocked its expression. Collectively, our results suggested that the RP11-670E13.6/miR-663a/CDK4 and RP11-670E13.6/miR-663a/CDK6 axis, which may function as competitive endogenous RNA networks, played important roles in UVB-induced cellular senescence.
Highlights
The aging of human skin is caused by genetic and environmental factors
We found that the ratio of senescent cells markedly increased following transfection with small-interfering RNA targeting RP11-670E13.6 compared with that of the negative controls (NC) [21]
Because the mRNA expressions of many genes involving in DNA replication and double-strand breaks (DSBs) repair were significantly altered by RP11-670E13.6 depletion, we further examined whether RP11-670E13.6 played a role in the DNA damage response (DDR) in UVB irradiated HDFs
Summary
The aging of human skin is caused by genetic and environmental factors. DNA photodamage and UV-generated reactive oxygen species (ROS) are the initial molecular events that lead to most of the typical histological and clinical manifestations of skin aging. Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length, have been shown to play crucial regulatory roles in numerous biological processes [9, 10]. MicroRNAs (miRNAs) are a class of short noncoding RNAs (~22 nucleotides in length) [12, 13] that inhibit the expression of target genes by binding to the 3′ untranslated region (3′-UTR) of specific mRNA targets and degrade the mRNA or suppress translation [14].
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