Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several ...Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.展开更多
As members of the Kruppel-like transcription factor family,KLF4 and KLF5 play critical roles in the development and progression of breast cancer,yet their functions are complex.KLF4 exhibits a dual role:on one hand,it...As members of the Kruppel-like transcription factor family,KLF4 and KLF5 play critical roles in the development and progression of breast cancer,yet their functions are complex.KLF4 exhibits a dual role:on one hand,it inhibits metastasis by suppressing epithelial-mesenchymal transition(EMT)and activating E-cadherin transcription;on the other hand,it can sustain tumor stem cell properties to promote progression.Its tumor-suppressive or tumor-promoting effects are highly dependent on the status of p21 and the cellular microenvironment.KLF5 is significantly overexpressed in basal-like breast cancer(BLBC)and triple-negative breast cancer(TNBC),promoting tumor proliferation and metastasis by regulating the cell cycle(inducing Cyclin D1 and inhibiting p27),maintaining stemness(activating Slug/Nanog),and forming a positive feedback loop with KLF5-XPO1.Clinical studies have demonstrated that overexpression of KLF4 is associated with poor prognosis in patients,while small-molecule inhibitors targeting KLF5(such as mifepristone and CDK7/BRD4 inhibitors)can inhibit the growth of triple-negative breast cancer(TNBC).Both KLF4 and KLF5 influence breast cancer heterogeneity and treatment response by regulating key signaling pathways.Future research should further elucidate their environment-dependent mechanisms to develop precise targeting strategies.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81872686 and 82173611)the National Key Research and Development Program of China(Grant No.2018YFC2000703)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)。
文摘Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.
文摘As members of the Kruppel-like transcription factor family,KLF4 and KLF5 play critical roles in the development and progression of breast cancer,yet their functions are complex.KLF4 exhibits a dual role:on one hand,it inhibits metastasis by suppressing epithelial-mesenchymal transition(EMT)and activating E-cadherin transcription;on the other hand,it can sustain tumor stem cell properties to promote progression.Its tumor-suppressive or tumor-promoting effects are highly dependent on the status of p21 and the cellular microenvironment.KLF5 is significantly overexpressed in basal-like breast cancer(BLBC)and triple-negative breast cancer(TNBC),promoting tumor proliferation and metastasis by regulating the cell cycle(inducing Cyclin D1 and inhibiting p27),maintaining stemness(activating Slug/Nanog),and forming a positive feedback loop with KLF5-XPO1.Clinical studies have demonstrated that overexpression of KLF4 is associated with poor prognosis in patients,while small-molecule inhibitors targeting KLF5(such as mifepristone and CDK7/BRD4 inhibitors)can inhibit the growth of triple-negative breast cancer(TNBC).Both KLF4 and KLF5 influence breast cancer heterogeneity and treatment response by regulating key signaling pathways.Future research should further elucidate their environment-dependent mechanisms to develop precise targeting strategies.
