MiR-194-5p suppresses the warburg effect in ovarian cancer cells through the IGF1R/PI3K/AKT axis

Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor(IGF1R).In this study,we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells.Methods:The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection.ATP generation,glucose uptake,lactate production and extracellular acidification rate(ECAR)assay were used to analyze the effects of aerobic glycolysis in ovarian cancer cells.Gene expression was analyzed by quantitative polymerase chain reaction(qPCR)and western blot.Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancer tissues.Results:Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATP generation,glucose uptake,lactate production,and ECAR and inhibits both the mRNA and protein expression of PKM2,LDHA,GLUT1,and GLUT3.While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway,whose activation can sustain aerobic glycolysis in cancer cells,and the knockdown of miR-194-5p expression promoted the activation of the PI3K/AKT pathway.Conclusion:Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKT pathway,which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.

Three-dimensional oxygen-doped porous graphene:Sodium chloridetemplate preparation,structural characterization and supercapacitor performances

Supercapacitor is a new type of energy storage device,which has the advantages of high-power property and long cycle life.In this study,three-dimensional graphene(3 D-GN)with oxygen doping and porous structure was prepared from graphene oxide(GO)by an inexpensive sodium chloride(NaCl)template,as a promising electrode material for the supercapacitor.The structure,morphology,specific surface area,pore size,of the sample were characterized by XRD,SEM,TEM and BET techniques.The electrochemical performances of the sample were tested by CV and CDC techniques.The 3 D-GE product is a threedimensional nano material with hierarchical porous structures,its specific surface area is much larger than that of routine stacked graphene(GN),and it contains a large number of mesoporous and macropores,a small amount of micropores.The capacitance characteristics of the 3 D-GN electrode material are excellent,showing high specific capacitance(173.5 F·g^(-1)at 1 A·g^(-1)),good rate performance(109.2 F·g^(-1)at 8 A·g^(-1))and long cycle life(88%capacitance retention after 10,000 cycles at 8 A·g^(-1))

Application of integrated formation evaluation and three-dimensional modeling in shale gas prospect identification

Identifying the shale gas prospect is crucial for gas extraction from such reservoirs.Junggar Basin(in Northwest China)is widely considered to have high potential as a shale gas resource,and the Jurassic,the most significant gas source strata,is considered as prospective for shale gas exploration and development.This study evaluated the Lower Jurassic Badaowan Formation shale gas potential combined with geochemical,geological,and well logging data,and built a three-dimensional(3D)model to exhibit favorable shale gas prospects.In addition,methane sorption capacity was tested for verifying the prospects.The Badaowan shale had an average total organic carbon(TOC)content of 1.30 wt.%and vitrinite reflectance(Ro)ranging from 0.47%to 0.81%with dominated type III organic matter(OM).X-ray diffraction(XRD)analyses showed that mineral composition of Badaowan shale was fairly homogeneous and dominated by clay and brittle minerals.67 wells were used to identify prospective shale intervals and to delineate the area of prospects.Consequently,three Badaowan shale gas prospects in the Junggar Basin were identified:the northwestern margin prospect,eastern Central Depression prospect and Wulungu Depression prospect.The middle interval of the northwestern margin prospect was considered to be the most favorable exploration target benefitted by wide distribution and high lateral continuity.Generally,methane sorption capacity of the Badaowan shale was comparable to that of the typical gas shales with similar TOC content,showing a feasible gas potential.

Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to organs.The dysregulation of double-negative(DN)T cells is considered as a crucial commander during SLE.Neddylation,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune response.However,the function of neddylation in SLE is still unknown.Here,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development.Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus mice.Then double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression.Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression.Clinically,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was reduced.Moreover,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels.Meantime,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients.Altogether,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.