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
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
Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between t...Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.展开更多
目的探讨维生素E干预治疗对脑梗死患者尿液中8-异前列腺素F_(2α)(8-iso-PGF_(2α))含量的影响。方法选取14例脑梗死患者作为治疗组,给予维生素E(300mg/d)治疗;另选取14例年龄、性别、血压、血脂、病灶部位及脑梗死程度与治疗组无显著...目的探讨维生素E干预治疗对脑梗死患者尿液中8-异前列腺素F_(2α)(8-iso-PGF_(2α))含量的影响。方法选取14例脑梗死患者作为治疗组,给予维生素E(300mg/d)治疗;另选取14例年龄、性别、血压、血脂、病灶部位及脑梗死程度与治疗组无显著差异的脑梗死患者作为对照组,不给予维生素E治疗。收集所有患者发病24h内和发病14天时的尿样和血清,测定尿样中8-iso-PGF_(2α)及血清中维生素E浓度。结果治疗组患者14天时尿液中8-iso-PGF_(2α)的浓度均显著低于对照组(85.20±9.17 vs 91.36±4.24ng/ mmol creatinine,P<0.05);而血清中维生素E的浓度显著高于对照组(15.56±6.98 vs 10.91±4.36μmol/L,P<0.05)。静脉血中低密度脂蛋白(LDL)中的总胆固醇、LDL三酰甘油和LDL游离胆固醇在治疗组与对照组间无显著性差异(分别为5.08±0.61 vs 4.72±0.61mmol/L,0.88±0.06 vs 0.84±0.03 mmol/L,1.72±0.41 vs 1.75±0.92mmol/L,P>0.05)。结论维生素E干预治疗可以降低急性期脑梗死患者尿液中8-iso-PGF_(2α)含量,减轻其体内的氧化压力。展开更多
The E2F/DP pathway is a widely conserved regulatory mechanism in pluricellular organisms.The family of E2F and DP transcription factors was originally described having a role in the transition from the G1 to the S pha...The E2F/DP pathway is a widely conserved regulatory mechanism in pluricellular organisms.The family of E2F and DP transcription factors was originally described having a role in the transition from the G1 to the S phase of the cell cycle.However,the discovery of hundreds of possible gene targets and their involvement in many other biochemical processes,soon showed that they participated in cell development and differentiation,chromatin remodeling,DNA repair and others.The E2F/DP transcription factors can act as either activators or repressors of transcription depending on their association to other regulatory proteins,particularly the retinoblastoma protein,or even depending to their protein structure that can define their role.In plants the E2F/DP pathway also regulates endoreduplication,a process present along the life cycle,from organ elongation to root differentiation and reproduction.These transcription factors also help plant cells to respond to environmental disturbances such as those caused by different types of radiation,or by pathogens.This review focuses on the“so called”non-canonical functions of the E2F/DP family proteins in animal and plant cells,that are in fact essential activities that connect regulatory circuits among multiple metabolic pathways by means of their atypical functions.展开更多
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.
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Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.
文摘目的探讨维生素E干预治疗对脑梗死患者尿液中8-异前列腺素F_(2α)(8-iso-PGF_(2α))含量的影响。方法选取14例脑梗死患者作为治疗组,给予维生素E(300mg/d)治疗;另选取14例年龄、性别、血压、血脂、病灶部位及脑梗死程度与治疗组无显著差异的脑梗死患者作为对照组,不给予维生素E治疗。收集所有患者发病24h内和发病14天时的尿样和血清,测定尿样中8-iso-PGF_(2α)及血清中维生素E浓度。结果治疗组患者14天时尿液中8-iso-PGF_(2α)的浓度均显著低于对照组(85.20±9.17 vs 91.36±4.24ng/ mmol creatinine,P<0.05);而血清中维生素E的浓度显著高于对照组(15.56±6.98 vs 10.91±4.36μmol/L,P<0.05)。静脉血中低密度脂蛋白(LDL)中的总胆固醇、LDL三酰甘油和LDL游离胆固醇在治疗组与对照组间无显著性差异(分别为5.08±0.61 vs 4.72±0.61mmol/L,0.88±0.06 vs 0.84±0.03 mmol/L,1.72±0.41 vs 1.75±0.92mmol/L,P>0.05)。结论维生素E干预治疗可以降低急性期脑梗死患者尿液中8-iso-PGF_(2α)含量,减轻其体内的氧化压力。
基金This work was supported by Consejo Nacional de Ciencia y Tecnología[Grant No.CB220661,PostgraduateMobility grants to V.A.S.C.and SNI III grant to S.R.R.]and Universidad Nacional Autónoma de México[DGAPA-PAPIIT IN215316,PAIP 5000-9124,PAIP 5000-9130 and PAEP-UNAM grant to V.A.S.C.].
文摘The E2F/DP pathway is a widely conserved regulatory mechanism in pluricellular organisms.The family of E2F and DP transcription factors was originally described having a role in the transition from the G1 to the S phase of the cell cycle.However,the discovery of hundreds of possible gene targets and their involvement in many other biochemical processes,soon showed that they participated in cell development and differentiation,chromatin remodeling,DNA repair and others.The E2F/DP transcription factors can act as either activators or repressors of transcription depending on their association to other regulatory proteins,particularly the retinoblastoma protein,or even depending to their protein structure that can define their role.In plants the E2F/DP pathway also regulates endoreduplication,a process present along the life cycle,from organ elongation to root differentiation and reproduction.These transcription factors also help plant cells to respond to environmental disturbances such as those caused by different types of radiation,or by pathogens.This review focuses on the“so called”non-canonical functions of the E2F/DP family proteins in animal and plant cells,that are in fact essential activities that connect regulatory circuits among multiple metabolic pathways by means of their atypical functions.
