LSD1 interacting with HSP90 promotes skin wound healing by inducing metabolic reprogramming of hair follicle stem cells through the c-MYC/LDHA axis.

It has been demonstrated that hair follicle stem cells (HFSCs) can contribute to wound closure and repair. However, the specific mechanism remains unclear due to the complexity of the wound repair process. Lysine-specific demethylase 1 (LSD1), an important gene for the regulation of stem cell differentiation, has been reported to participate in wound healing regulation. Heat shock protein 90 (HSP90), a chaperone protein, is recently discovered to be a driver gene for wound healing. This study explored the molecular mechanisms by which the binding between LSD1 and HSP90 affects the role of HFSCs during skin wound healing. Following bioinformatics analysis, the key genes acting on HFSCs were identified. The expression of LSD1, HSP90, and c-MYC was found to be upregulated in differentiated HFSCs. Analysis of their binding affinity revealed that LSD1 interacted with HSP90 to enhance the stability of the transcription factor c-MYC. Lactate dehydrogenase A (LDHA) has been documented to be essential for HFSC activation. Therefore, we speculate that LDHA may induce the differentiation of HFSCs through glucose metabolism reprogramming. The results showed that c-MYC activated LDHA activity to promote glycolytic metabolism, proliferation, and differentiation of HFSCs. Finally, in vivo animal experiments further confirmed that LSD1 induced skin wound healing in mice via the HSP90/c-MYC/LDHA axis. From our data, we conclude that LSD1 interacting with HSP90 accelerates skin wound healing by inducing HFSC glycolytic metabolism, proliferation, and differentiation via c-MYC/LDHA axis.

LncRNA CRNDE inhibits cardiomyocytes apoptosis by YAP1 in myocardial ischaemia/reperfusion injury.

BACKGROUND: Cardiomyocytes apoptosis is the basic pathological process of myocardial ischaemia/reperfusion (MI/R) injury, so inhibiting apoptosis of cardiomyocytes can effectively improve MI/R injury. Long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) can inhibit cell apoptosis, but its specific role in MI/R injury has not been studied. The aim of this study is to explore the specific effect of lncRNA CRNDE on cardiomyocytes apoptosis. METHODS: MI/R model in vivo and hypoxia/re-oxygenation (H/R) model in vitro were constructed. Apoptotic levels were assessed by TUNEL staining assay. QRT-PCR was used to validate lncRNA CRNDE level in myocardial tissues and HL-1 cells. The protein expressions of YAP1, Bcl-2 and cleaved caspase-3 were detected by western blot analysis. Flow cytometry was used to determine the apoptosis rate of cardiomyocytes. RIP assay was used to detect the interaction between lncRNA CRNDE and YAP1. RESULTS: The extent of cardiomyocytes apoptosis was significantly increased, and the levels of lncRNA CRNDE, YAP1 and Bcl-2 were down-regulated, while cleaved caspase-3 expression was up-regulated in MI/R mice and H/R-treated HL-1 cells. The expressions of YAP1 and Bcl-2 were decreased, while the expression of cleaved caspase-3 was increased after the knockdown of lncRNA CRNDE. Furthermore, lncRNA CRNDE could bind to YAP1 and regulated the protein level of YAP1 by ubiquitination and proteasomal degradation pathway. After transfection of Si-YAP1 in the H/R-treated HL-1 cells transfected with pc-DNA CRNDE, the protein level of Bcl-2 was decreased, while cleaved caspase-3 expression and the apoptosis rate were increased. CONCLUSION: Our study suggested that lncRNA CRNDE could regulate YAP1 level by ubiquitination and proteasomal degradation pathway, thus inhibiting cardiomyocytes apoptosis in MI/R injury.

LncRNA NORAD engages in psoriasis by binding to miR-26a to regulate keratinocyte proliferation.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. It was reported that lncRNA Non-coding RNA-activated by DNA damage (NORAD) has potential regulatory effects on skin diseases. Our previous studies found that lncRNA NORAD was highly expressed and its potential target miR-26a was down-regulated in psoriasis model mice. Here, we aimed to investigate the role of NORAD in the development of psoriasis. METHODS: IL-22/LPS (interleukin-22/lipopolysaccharide)-stimulated HaCaT (human immortalized keratinocytes) cell model and imiquimod-induced mouse model were established. Keratin 6 (K6), Keratin 16 (K16), Keratin 17 (K17), and Cell division cycle 6 (CDC6) levels were detected by western blot. Cell activity was detected by CCK-8, MTT, and EdU assays. Quantitative real-time PCR was performed to examine the levels of NORAD, miR-26a, CDC6, K6, K16, and K17. Haematoxylin-eosin staining was applied to observe the degree of skin thickening and hyperplasia. Fluorescence in situ hybridization detects the location of NORAD. RNA immunoprecipitation, RNA pull-down, and Luciferase test were performed to detect the interaction between NORAD and miR-26a. RESULTS: In IL-22/LPS-stimulated HaCaT cells, NORAD, CDC6, and keratinocyte proliferation-related proteins (K6, K16, and K17) were up-regulated and miR-26a was down-regulated. Cell survival and proliferation were also increased. However, the results were reversed after interference with NORAD. Also, in vitro experiments revealed that NORAD negatively regulated miR-26a. In IL-22/LPS-stimulated HaCaT cells and skin of imiquimod-induced mice, we found that lower NORAD resulted in an increase of miR-26a and a decrease of CDC6, further decreased levels of keratinocyte proliferation-related proteins (K6, K16, and K17).