RESUMEN
BACKGROUND: Psoriasis is a complex, chronic inflammatory skin disease with substantial negative effects on patient quality of life. Long non-coding RNAs (lncRNAs) are able to be involved in multitudes of cellular processes in diverse human diseases. This study aimed to investigate the potential involvement of lncRNA MIR31HG in HaCaT keratinocytes proliferation. RESULTS: The study showed that MIR31HG was significantly elevated in the lesional psoriatic skin compared with normal individuals' skin. Knockdown of MIR31HG inhibited HaCaT keratinocytes proliferation. Flow cytometry analysis showed that siRNA-mediated MIR31HG depletion induced cell cycle arrest in the G2/M phase. In addition, MIR31HG expression was found to be dependent on NF-κB activation. CONCLUSIONS: NF-κB activation mediated MIR31HG upregulation plays an important role in the regulation of HaCaT keratinocytes proliferation. It could be a potential diagnostic biomarker and therapeutic target for psoriasis.
Asunto(s)
Queratinocitos/metabolismo , Psoriasis/metabolismo , ARN Largo no Codificante/fisiología , Biomarcadores , Estudios de Casos y Controles , Proliferación Celular , Regulación de la Expresión Génica , Humanos , Queratinocitos/patología , Psoriasis/genética , Psoriasis/patología , Transducción de Señal , Regulación hacia ArribaRESUMEN
PURPOSE: The purpose this study is to investigate the impact of SIRT1 on the anti-HBV activity of IFN-α and further elucidate its underlying mechanism. METHODS: HepG2.2.15 cells stably transfected with HBV virus were chosen as the primary study subject. IFN-α was used to stimulate the cells and regulate the expression of SIRT1, and the JAK-STAT pathway and HBV-related indices were measured by qRT-PCR, Western blotting and ELISA. Immunofluorescence (IF) was used to detect the nuclear translocation of STAT1 and STAT2. Coimmunoprecipitation (Co-IP) was used to detect the binding of SIRT1 to HBV Polymerase (Pol). RESULTS: In HepG2.2.15 cells, we found changes in SIRT1 expression. We show that silencing SIRT1 promotes the IFN-α-triggered Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and consequently enhances the antiviral effects of IFN-α against HBV replication. Importantly, SIRT1 can interact with Pol and increase JAK-STAT activity by regulating Pol expression. Additionally, the inhibition of SIRT1 activity by treatment with the SIRT1 inhibitor selisistat enhanced the anti-HBV effect of IFN-α and JAK-STAT pathway activity. CONCLUSION: In conclusion, our results demonstrate that silencing SIRT1 activates the JAK-STAT pathway and enhances the anti-HBV activity of IFN-α by inhibiting Pol expression. This would be a promising therapeutic target to improve the efficacy of IFN-α in the treatment of CHB.
Asunto(s)
Quinasas Janus , Transducción de Señal , Quinasas Janus/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Virus de la Hepatitis B/fisiología , Factores de Transcripción STAT/metabolismo , Interferón-alfa/farmacología , Interferón-alfa/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismoRESUMEN
Anti-tuberculosis drug-induced liver injury (ADLI) is one of the main factors hindering the efficacy of routine chemotherapy against tuberculosis. Understanding the mechanism of ADLI will aid in the effective treatment of patients with tuberculosis. Recently, we found that the expression of hsa_circ_0093884, a circular RNA derived from the NAD-dependent deacetylase, sirtuin-1 (SIRT1), was down-regulated in ADLI. Hsa_circ_0093884 was negatively correlated with the NLR family pyrin domain containing 3 (NLRP3) inflammasome and its overexpression increased the expression levels of NLRP3, interleukin-1ß, and caspase-1. Mechanistically, RNA immunoprecipitation and immunofluorescence assays revealed that the ribosomal protein S3 (RPS3) could bind to hsa_circ_0093884 and SIRT1. Additionally, the expression of hsa_circ_0093884 was positively correlated with that of SIRT1, and the upregulation of hsa_circ_0093884 expression was crucial for the upregulation of SIRT1 expression. We confirmed that the mRNA and protein expression levels of SIRT1 were influenced by hsa_circ_0093884 and RPS3. Furthermore, hsa_circ_0093884 recruited RPS3 to increase SIRT1 mRNA and protein levels. Importantly, we found a marked decrease in the upregulating effect of hsa_circ_0093884 on SIRT1 owing to RPS3 depletion. To the best of our knowledge, this study is the first to reveal that hsa_circ_0093884 regulates SIRT1 expression and inhibits the inflammatory response by binding to RPS3 in ADLI, which may be used to develop novel strategies for ADLI treatment.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , MicroARNs , Proliferación Celular/genética , Hepatocitos/metabolismo , Humanos , Inflamación , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , ARN Mensajero , Proteínas de Unión al ARN , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismoRESUMEN
BACKGROUND: Psoriasis is a complex, chronic inflammatory skin disease with substantial negative effects on patient quality of life. Long non-coding RNAs (lncRNAs) are able to be involved in multitudes of cellular processes in diverse human diseases. This study aimed to investigate the potential involvement of lncRNA MIR31HG in HaCaT keratinocytes proliferation. RESULTS: The study showed that MIR31HG was significantly elevated in the lesional psoriatic skin compared with normal individuals' skin. Knockdown of MIR31HG inhibited HaCaT keratinocytes proliferation. Flow cytometry analysis showed that siRNA-mediated MIR31HG depletion induced cell cycle arrest in the G2/M phase. In addition, MIR31HG expression was found to be dependent on NF-κB activation. CONCLUSIONS: NF-κB activation mediated MIR31HG upregulation plays an important role in the regulation of HaCaT keratinocytes proliferation. It could be a potential diagnostic biomarker and therapeutic target for psoriasis.