BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the ...BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.展开更多
The predisposition to stroke might involve interactive effects among variants in several genes.We tested this hypothesis by examining the influence of polymorphisms in methylenetetrahydrofolate reductase（MTHFR）（C6...The predisposition to stroke might involve interactive effects among variants in several genes.We tested this hypothesis by examining the influence of polymorphisms in methylenetetrahydrofolate reductase（MTHFR）（C677T） and prothrombin（F2）（G20210A） as risk factors for stroke in Morocco.The polymerase chain reaction-restriction fragment length polymorphism methods were used to analyze DNA from 91 stroke patients and 182 controls.Association between the two polymorphisms and the risk of stroke was estimated by four-level models for the analysis of genetic interaction.Neither the MTHFR 677TT nor the F2 20210GA genotype showed any significant association compared to the MTHFR CC and F2 GG genotypes,respectively.An interactive effect between the MTHFR 677TT and F2 20210GA polymorphisms showed an increased risk of stroke.The odds ratios,in univariate and multivariate analysis,for the combined polymorphisms were 4.99（95% CI,1.75–14.2,P = 0.001） and 5.29（95% CI,1.63–17.1,P = 0.005）,respectively.展开更多
BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its ro...BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.展开更多
Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,de...Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,despite its established oncogenic functions in other cancers.Therefore,this study sought to characterize the oncogenic role and molecular mechanism of DDX11-AS1 in glioma.Methods:DDX11-AS1 expression levels were analyzed in clinical surgical glioma specimens and publicly available datasets.The functional roles of DDX11-AS1 on glioma cell proliferation and migration were investigated using in vitro knockdown and overexpression assays.In vivo tumor growth was assessed using orthotopic glioma-bearing mouse models.To elucidate the regulatory axis involving DDX11-AS1,miR-1183,and E2F transcription factor 7(E2F7),we performed competitive endogenous RNA(ceRNA)analysis and conducted functional rescue experiments via miR-1183 inhibition.Results:DDX11-AS1 expression was markedly upregulated in clinical glioma specimens.Functionally,DDX11-AS1 knockdown significantly suppressed glioma cell proliferation and migration in vitro,while its overexpression exacerbated these malignant phenotypes.Orthotopic glioma-bearingmouse models confirmed that DDX11-AS1 drives in vivo glioma tumor growth.Mechanistically,DDX11-AS1 functions as a ceRNA by competitively interacting with miR-1183.Critically,inhibition of miR-1183 rescued the suppressive effects of DDX11-AS1 knockdown on glioma tumorigenic phenotypes and restored E2F7 expression levels.Conclusions:This study demonstrates that lncRNA DDX11-AS1 promotes glioma progression by regulating the miR-1183/E2F7 axis,indicating a potential therapeutic target for glioma.展开更多
文摘BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.
文摘The predisposition to stroke might involve interactive effects among variants in several genes.We tested this hypothesis by examining the influence of polymorphisms in methylenetetrahydrofolate reductase（MTHFR）（C677T） and prothrombin（F2）（G20210A） as risk factors for stroke in Morocco.The polymerase chain reaction-restriction fragment length polymorphism methods were used to analyze DNA from 91 stroke patients and 182 controls.Association between the two polymorphisms and the risk of stroke was estimated by four-level models for the analysis of genetic interaction.Neither the MTHFR 677TT nor the F2 20210GA genotype showed any significant association compared to the MTHFR CC and F2 GG genotypes,respectively.An interactive effect between the MTHFR 677TT and F2 20210GA polymorphisms showed an increased risk of stroke.The odds ratios,in univariate and multivariate analysis,for the combined polymorphisms were 4.99（95% CI,1.75–14.2,P = 0.001） and 5.29（95% CI,1.63–17.1,P = 0.005）,respectively.
文摘BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.
基金supported by Shenzhen Science and Technology Program(JCYJ20220530152614033,JCYJ20230807142213027)Funding Statement Special Fund for Economic and Technological Development in Longgang District,Shenzhen(LGKCYLWS2023028).
文摘Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,despite its established oncogenic functions in other cancers.Therefore,this study sought to characterize the oncogenic role and molecular mechanism of DDX11-AS1 in glioma.Methods:DDX11-AS1 expression levels were analyzed in clinical surgical glioma specimens and publicly available datasets.The functional roles of DDX11-AS1 on glioma cell proliferation and migration were investigated using in vitro knockdown and overexpression assays.In vivo tumor growth was assessed using orthotopic glioma-bearing mouse models.To elucidate the regulatory axis involving DDX11-AS1,miR-1183,and E2F transcription factor 7(E2F7),we performed competitive endogenous RNA(ceRNA)analysis and conducted functional rescue experiments via miR-1183 inhibition.Results:DDX11-AS1 expression was markedly upregulated in clinical glioma specimens.Functionally,DDX11-AS1 knockdown significantly suppressed glioma cell proliferation and migration in vitro,while its overexpression exacerbated these malignant phenotypes.Orthotopic glioma-bearingmouse models confirmed that DDX11-AS1 drives in vivo glioma tumor growth.Mechanistically,DDX11-AS1 functions as a ceRNA by competitively interacting with miR-1183.Critically,inhibition of miR-1183 rescued the suppressive effects of DDX11-AS1 knockdown on glioma tumorigenic phenotypes and restored E2F7 expression levels.Conclusions:This study demonstrates that lncRNA DDX11-AS1 promotes glioma progression by regulating the miR-1183/E2F7 axis,indicating a potential therapeutic target for glioma.
