Abstract
In this study, we obtained the RNA expression data of murine skin tissues of control, and UVB irradiated groups. After the re-annotation of lncRNAs, a gene expression similarity analysis was done by WGCNA. The target mRNA prediction of lncRNAs, miRNAs, and ceRNA regulatory networks were constructed by five lncRNAs, 14 miRNAs and 54 mRNAs, respectively. Based on the ceRNA network of UVB-induced skin lesions, it was evident that the dysregulation of Meg3 has critical effects on the UVB-induced inflammatory lesion of murine skin tissues. The overexpression of Meg3 after UVB irradiation was observed in primary murine skin fibroblasts, and the up-regulated Meg3 expression was related to the activation of the inflammatory cytokines. These functional experiments demonstrated that the RNA silencing of Meg3 in murine skin fibroblasts could suppress the expression of the cytokines (in vitro) and UVB-induced skin lesions (in vivo). Moreover, the Meg3 functioned as a competing endogenous RNA (ceRNA) that acted as a sponge for miR-93-5p and thereby modulated the expression of Epiregulin (Ereg). Our results proved that Meg3 was involved in UVB-induced skin inflammation and that the ceRNA networks, which includes miR-93-5p and Ereg, could prove to be a potential therapeutic target for UVB-induced skin damage.
Highlights
Skin exposure to ultraviolet radiation (UV) is necessary to enhance vitamin D production; excessive exposure to UV cause skin malignancies [1,2,3]
As compared to wild-type Meg3, the mutant-type Meg3 levels significantly declined in the anti-ago2 group. These results suggested that miR93-5p was a direct target miRNA of lncRNA Meg3, and their interactions result in RNAinduced silencing complexes (RISCs)-mediated degradation via an ago2-dependent manner
LncRNA-PRINS could increase the sensitivity of keratinocytes to spontaneous apoptosis by up-regulating the expression of GIP3, which promoted the proliferation of keratinocytes, and affected the development of psoriasis
Summary
Skin exposure to ultraviolet radiation (UV) is necessary to enhance vitamin D production; excessive exposure to UV cause skin malignancies [1,2,3]. The lncRNA with the sequence lengths longer than 200 nucleotides could regulate gene expression via a cis- or trans- mechanism, which allows it to associate with RNA and de-stabilizes the target proteins [8,9,10,11,12,13,14,15,16,17]. MicroRNA (miRNA) exerts a regulatory role in skin inflammations by mediating target mRNA degradation or inhibiting the mRNA translation [20,21,22,23,24,25]. The latest research indicates that the ceRNA (competing endogenous RNA) network constitute the key regulatory mechanism in the www.aging-us.com pathogenesis and development of skin disorders. Most miRNAs could suppress the MEG3 expression via post-transcription regulation which competes with the endogenous RNA mechanism [30,31,32,33,34]. MEG3 could activate or inhibit multiple signaling pathways, i.e., p53, TGFβ, Rb, and EZH2; and the dysregulation of MEG3 expression was typical to solid tumors, inflammation, and autoimmune disease [34,35,36,37,38]
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