Objective:Oxaliplatin(OXA)and 5-fluorouracil(5-FU)are 2 commonly used chemotherapeutic agents for colorectal cancer(CRC).MicroRNAs(miRNAs,miRs)play crucial roles in the development of chemoresistance in various cancer...Objective:Oxaliplatin(OXA)and 5-fluorouracil(5-FU)are 2 commonly used chemotherapeutic agents for colorectal cancer(CRC).MicroRNAs(miRNAs,miRs)play crucial roles in the development of chemoresistance in various cancers.However,the role and mechanism of miR-224-5p in regulating CRC chemoresistance remain unclear.This study aims to investigate the function of miR-224-5p in chemoresistant CRC cells and the underlying mechanisms.Methods:CRC datasets GSE28702 and GSE69657 were downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed miRNAs between drug sensitive and resistant groups(OXA or 5-FU)were analyzed,and miR-224-5p was identified as the target miRNA.Chemoresistant cell lines HCT15-OXR,HCT15-5-FU,SW480-OXR,and SW480-5-FU were established.Transient transfections were performed using miR-224-5p mimics,inhibitors,and their respective negative controls(control mimic,control inhibitor)in these cell lines.Cells were treated with different concentrations of OXA or 5-FU post-transfection,and the half-maximal inhibitory concentration(IC_(50))was determined using the cell counting kit-8(CCK-8)assay.Cell proliferation was assessed by CCK-8 and colony formation assays.The expression levels of miR-224-5p,LC3,and P62 were measured by real-time polymerase chain reaction(real-time PCR)and/or Western blotting.Autophagic flux was assessed using a tandem fluorescent-tagged LC3 reporter assay.TargetScan 8.0,miRTarBase,miRPathDB,and HADb were used to predict B-cell lymphoma-2(Bcl-2)as a potential miR-244-5p target,which was further validated by dual luciferase reporter assays.Results:Chemoresistant CRC cells exhibited down-regulated miR-224-5p expression,whereas up-regulation of miR-224-5p enhanced chemotherapy sensitivity.Exposure to OXA or 5-FU significantly increased autophagic activity in chemoresistant CRC cells,which was reversed by miR-224-5p overexpression.Dual-luciferase assays verified Bcl-2 as a direct target of miR-224-5p.Conclusion:MiR-224-5p regulates chemoresistance in CRC by modulating autophagy through direct targeting of Bcl-2.展开更多
Objective:To explore the relationship between cancer awareness and the survival of the patients with non-small cell lung carcinoma(NSCLC).Methods:A total of 865 NSCLC patients were screened for the risk factors,includ...Objective:To explore the relationship between cancer awareness and the survival of the patients with non-small cell lung carcinoma(NSCLC).Methods:A total of 865 NSCLC patients were screened for the risk factors,including age,gender,address,tumor/lymph nodes/metastasis(TNM)stage,and cancer awareness.Survival of the patients was calculated by Kaplan-Meier method and Cox regression analysis.Results:After an average observation time of 304 d(ranging from 0 to 4718 d),62 of the 394 patients in the cancer awareness group survived,whereas 26 of the 471 patients in the cancer concealment group survived.Cancer-specific and all-cause survival was poorer in the cancer concealment group(P<0.001 for each,log-rank test).Cox multivariate regression analysis showed that cancer concealment displayed significantly lower cancer-specific survival[hazard ratio(HR)=1.534,95%con fi dence interval(CI)1.320 to 1.784,P<0.001]and all-cause survival(HR=1.558,95%CI 1.346 to 1.803,P<0.001).Conclusion:Cancer concealment is associated with a poor survival of NSCLC patients,which may prohibit the patients from obtaining the real“right to survival”.展开更多
基金supported by the National Natural Science Foundation(82072729)Wuhan Municipal Health Commission Medical Research Project(WX19Q30),China。
文摘Objective:Oxaliplatin(OXA)and 5-fluorouracil(5-FU)are 2 commonly used chemotherapeutic agents for colorectal cancer(CRC).MicroRNAs(miRNAs,miRs)play crucial roles in the development of chemoresistance in various cancers.However,the role and mechanism of miR-224-5p in regulating CRC chemoresistance remain unclear.This study aims to investigate the function of miR-224-5p in chemoresistant CRC cells and the underlying mechanisms.Methods:CRC datasets GSE28702 and GSE69657 were downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed miRNAs between drug sensitive and resistant groups(OXA or 5-FU)were analyzed,and miR-224-5p was identified as the target miRNA.Chemoresistant cell lines HCT15-OXR,HCT15-5-FU,SW480-OXR,and SW480-5-FU were established.Transient transfections were performed using miR-224-5p mimics,inhibitors,and their respective negative controls(control mimic,control inhibitor)in these cell lines.Cells were treated with different concentrations of OXA or 5-FU post-transfection,and the half-maximal inhibitory concentration(IC_(50))was determined using the cell counting kit-8(CCK-8)assay.Cell proliferation was assessed by CCK-8 and colony formation assays.The expression levels of miR-224-5p,LC3,and P62 were measured by real-time polymerase chain reaction(real-time PCR)and/or Western blotting.Autophagic flux was assessed using a tandem fluorescent-tagged LC3 reporter assay.TargetScan 8.0,miRTarBase,miRPathDB,and HADb were used to predict B-cell lymphoma-2(Bcl-2)as a potential miR-244-5p target,which was further validated by dual luciferase reporter assays.Results:Chemoresistant CRC cells exhibited down-regulated miR-224-5p expression,whereas up-regulation of miR-224-5p enhanced chemotherapy sensitivity.Exposure to OXA or 5-FU significantly increased autophagic activity in chemoresistant CRC cells,which was reversed by miR-224-5p overexpression.Dual-luciferase assays verified Bcl-2 as a direct target of miR-224-5p.Conclusion:MiR-224-5p regulates chemoresistance in CRC by modulating autophagy through direct targeting of Bcl-2.
基金supported by the National Natural Science Foundation of China(30872463)the Natural Science Foundation of Hunan Province,P.R.China(07JJ5016)the Scientific Research Fund from the Department of Public Health of Hunan Province,P.R.China(C2009-010)
基金supported by the National Natural Science Foundation of China(81572870)
文摘Objective:To explore the relationship between cancer awareness and the survival of the patients with non-small cell lung carcinoma(NSCLC).Methods:A total of 865 NSCLC patients were screened for the risk factors,including age,gender,address,tumor/lymph nodes/metastasis(TNM)stage,and cancer awareness.Survival of the patients was calculated by Kaplan-Meier method and Cox regression analysis.Results:After an average observation time of 304 d(ranging from 0 to 4718 d),62 of the 394 patients in the cancer awareness group survived,whereas 26 of the 471 patients in the cancer concealment group survived.Cancer-specific and all-cause survival was poorer in the cancer concealment group(P<0.001 for each,log-rank test).Cox multivariate regression analysis showed that cancer concealment displayed significantly lower cancer-specific survival[hazard ratio(HR)=1.534,95%con fi dence interval(CI)1.320 to 1.784,P<0.001]and all-cause survival(HR=1.558,95%CI 1.346 to 1.803,P<0.001).Conclusion:Cancer concealment is associated with a poor survival of NSCLC patients,which may prohibit the patients from obtaining the real“right to survival”.
