LncRNA RP11-670E13.6, interacted with hnRNPH, delays cellular senescence by sponging microRNA-663a in UVB damaged dermal fibroblasts

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 <i>RP11-670E13.6</i> was up-regulated and delayed cellular senescence in UVB-irradiated primary human dermal fibroblasts. Here, we performed further investigations of <i>RP11-670E13.6</i> function. The results showed that this lncRNA directly bound to <i>miR-663a</i> and functioned as a sponge for <i>miR-663a</i> to modulate the derepression of Cdk4 and Cdk6, thereby delaying cellular senescence during UV irradiation-induced skin photoaging. Moreover, we found that <i>RP11-670E13.6</i> may facilitate DNA damage repair by increasing ATM and γH2A.X levels. In addition, heterogeneous nuclear ribonucleoprotein H physically interacted with <i>RP11-670E13.6</i> and blocked its expression. Collectively, our results suggested that the <i>RP11-670E13.6/miR-663a</i>/<i>CDK4</i> and <i>RP11-670E13.6/miR-663a</i>/<i>CDK6</i> axis, which may function as competitive endogenous RNA networks, played important roles in UVB-induced cellular senescence.