LncRNA RP11-670E13.6, interacted with hnRNPH, delays cellular senescence by sponging microRNA-663a in UVB damage dermal fibroblasts
LncRNA RP11-670E13.6, interacted with hnRNPH, delays cellular senescence by sponging microRNA-663a in UVB damage dermal fibroblasts
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DOI：
10.18632/aging.102159
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发表时间：
2019-08-31
期刊：
影响因子：
5.2
通讯作者：
Yan, Yan
中科院分区：
文献类型：
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作者：
Li, Mengna;Li, Li;Yan, Yan
来自太阳的紫外线（UV）照射是皮肤过早老化的主要病因因素。长链非编码RNA（lncRNA）参与多种生物学过程，其在紫外线照射诱导的皮肤老化中的作用最近被描述。以前，我们发现lncRNA RP 11 - 670 E13.6在UVB照射的原代人真皮成纤维细胞中上调并延迟细胞衰老。在此，我们对RP 11 -670E13.6功能进行了进一步研究。结果表明，这种lncRNA直接与miR-663 a结合，并作为miR-663 a的海绵来调节Cdk 4和Cdk 6的去抑制，从而在UV辐射诱导的皮肤光老化过程中延缓细胞衰老。此外，我们发现RP 11 - 670 E13.6可能通过增加ATM和γ H2A.X水平促进DNA损伤修复。此外，异质核核糖核蛋白H与RP 11 -670E13.6物理相互作用并阻断其表达。综上所述，我们的研究结果表明RP 11 -670E13.6/miR-663 a/CDK 4和RP 11 -670E13.6/miR-663 a/CDK 6轴可能作为竞争性内源RNA网络在UVB诱导的细胞衰老中发挥重要作用。
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 miR663a 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 gamma H2A.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.