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 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.

Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases

“…[129] is reduced in the frontal cortex of ALS patients [129] TAF15 miR-17-92 CDKN1A/p21 regulates miRNA biogenesis to decrease genes related to cell proliferation [132] is reduced in an SOD1 G93A mouse model [133] hnRNP A1 miR-590-3p n.d. is cooperatively regulated in neuronal maintenance ? [135] is increased in the blood cells of FTD patients [135] hnRNP H miR-663a CDK4, CDK6 is cooperatively regulated in cellular senescence by targeting genes related to the cell cycle [137] is increased in the blood cells of ALS patients [138] RALY miR-483 ATP5I, ATP5G1, ATP5G3, CYC1 regulates miRNA biogenesis to decrease genes related to mitochondrial metabolism [140] n.d. miR-676 miR-877 RBM17 miR-150-5p VEGF-A is cooperatively regulated in genes related to growth factors [143] is reduced in the CSF of ALS patients [145] HuD miR-125a-5p CAMSAP3 cooperatively regulates circRNA in aging by targeting genes related to neuronal polarization [148] is reduced in aging mice [147] Matrin-3 miR-138-5p n.d.…”

“…One of the important functions of hnRNP H is splicing of the target transcripts, and the insolubility of hnRNP H correlates with that of the ALS-linked RBPs, such as TDP-43 and FUS [ 136 ]. hnRNP H directly binds to and suppresses a specific long noncoding RNA by functioning as a sponge of miR-663a [ 137 ]. The expression of miR-663a has been reported to be significantly increased in the blood of sporadic ALS patients [ 138 ].…”

Studies on the Regulatory Roles and Related Mechanisms of lncRNAs in the Nervous System

“…lncRNA HOTAIR upregulates autophagy to promote apoptosis and senescence of nucleus pulposus cells [ 10 ]. lncRNAs RP11-670E13.6 interact with hnRNPH and delay cell senescence by sponging microRNA-663a [ 11 ].…”

Circular RNA expression profiles significantly altered in UVA‑irradiated human dermal fibroblasts

“…Although the mechanism of photoaging remains to be fully elucidated, there have been numerous advances in recent years. For example, microRNA (miR)-377 have been reported to promote the senescence of human dermal fibroblasts by targeting DNA methyltransferase (6), whilst the long noncoding RNA (lncRNA) RP11-670E13.6 delays the senescence of UVB-irradiated dermal fibroblasts by sponging microRNA-663a (7). These previous studies have emphasized the essential roles of non-coding RNAs in photoaging.…”