BACKGROUND Diabetic macular edema(DME)is the most common cause of vision loss in people with diabetes.Tight junction disruption of the retinal pigment epithelium(RPE)cells has been reported to induce DME development.S...BACKGROUND Diabetic macular edema(DME)is the most common cause of vision loss in people with diabetes.Tight junction disruption of the retinal pigment epithelium(RPE)cells has been reported to induce DME development.SMAD-specific E3 ubiquitin protein ligase(SMURF)1 was associated with the tight junctions of cells.However,the mechanism of SMURF1 in the DME process remains unclear.AIM To investigate the role of SMURF1 in RPE cell tight junction during DME.METHODS ARPE-19 cells treated with high glucose(HG)and desferrioxamine mesylate(DFX)for establishment of the DME cell model.DME mice models were constructed by streptozotocin induction.The trans-epithelial electrical resistance and permeability of RPE cells were analyzed.The expressions of tight junction-related and autophagy-related proteins were determined.The interaction between insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)and SMURF1 mRNA was verified by RNA immunoprecipitation(RIP).SMURF1 N6-methyladenosine(m6A)level was detected by methylated RIP.RESULTS SMURF1 and vascular endothelial growth factor(VEGF)were upregulated in DME.SMURF1 knockdown reduced HG/DFX-induced autophagy,which protected RPE cell tight junctions and ameliorated retinal damage in DME mice.SMURF1 activated the Wnt/β-catenin-VEGF signaling pathway by promoting WNT inhibitory factor(WIF)1 ubiquitination and degradation.IGF2BP2 upregulated SMURF1 expression in an m6A modification-dependent manner.CONCLUSION M6A-modified SMURF1 promoted WIF1 ubiquitination and degradation,which activated autophagy to inhibit RPE cell tight junctions,ultimately promoting DME progression.展开更多
The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and deaths.While the direct effects of the virus are cri...The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and deaths.While the direct effects of the virus are critical,the interplay between SARS-CoV-2 and cellular host factors significantly impacts the replication cycle of the virus and the clinical severity of COVID-19.This review provides a comprehensive analysis of hostpathogen interactions,focusing on the functional roles and regulatory mechanisms of SARS-CoV-2 viral proteins.We systematically review the literature to detail how SARS-CoV-2 engages with host cellular machinery,with a specific emphasis on their modulation by E3 ubiquitin ligases.By dissecting these intricate interactions and the impact of E3 ligases on SARS-CoV-2 infection,we aimto uncover novel therapeutic opportunities and strategies to effectively combat COVID-19.展开更多
Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusiv...Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.展开更多
基金Supported by Natural Science Foundation of Guangdong Province,No.2022A1515012346.
文摘BACKGROUND Diabetic macular edema(DME)is the most common cause of vision loss in people with diabetes.Tight junction disruption of the retinal pigment epithelium(RPE)cells has been reported to induce DME development.SMAD-specific E3 ubiquitin protein ligase(SMURF)1 was associated with the tight junctions of cells.However,the mechanism of SMURF1 in the DME process remains unclear.AIM To investigate the role of SMURF1 in RPE cell tight junction during DME.METHODS ARPE-19 cells treated with high glucose(HG)and desferrioxamine mesylate(DFX)for establishment of the DME cell model.DME mice models were constructed by streptozotocin induction.The trans-epithelial electrical resistance and permeability of RPE cells were analyzed.The expressions of tight junction-related and autophagy-related proteins were determined.The interaction between insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)and SMURF1 mRNA was verified by RNA immunoprecipitation(RIP).SMURF1 N6-methyladenosine(m6A)level was detected by methylated RIP.RESULTS SMURF1 and vascular endothelial growth factor(VEGF)were upregulated in DME.SMURF1 knockdown reduced HG/DFX-induced autophagy,which protected RPE cell tight junctions and ameliorated retinal damage in DME mice.SMURF1 activated the Wnt/β-catenin-VEGF signaling pathway by promoting WNT inhibitory factor(WIF)1 ubiquitination and degradation.IGF2BP2 upregulated SMURF1 expression in an m6A modification-dependent manner.CONCLUSION M6A-modified SMURF1 promoted WIF1 ubiquitination and degradation,which activated autophagy to inhibit RPE cell tight junctions,ultimately promoting DME progression.
文摘The COVID-19 pandemic,caused by the newly emerged coronavirus SARS-CoV-2,has resulted in unprecedented global health challenges,including millions of infections and deaths.While the direct effects of the virus are critical,the interplay between SARS-CoV-2 and cellular host factors significantly impacts the replication cycle of the virus and the clinical severity of COVID-19.This review provides a comprehensive analysis of hostpathogen interactions,focusing on the functional roles and regulatory mechanisms of SARS-CoV-2 viral proteins.We systematically review the literature to detail how SARS-CoV-2 engages with host cellular machinery,with a specific emphasis on their modulation by E3 ubiquitin ligases.By dissecting these intricate interactions and the impact of E3 ligases on SARS-CoV-2 infection,we aimto uncover novel therapeutic opportunities and strategies to effectively combat COVID-19.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010403,Ning Lyu)Natural Science Foundation of Guangdong Province,China(No.1914050001553,Dong Chen).
文摘Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.
