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
Warfarin is a commonly used anticoagulant with a narrow therapeutic range and risk of hemorrhagic complications. After CYP2C9 and VKORC1, CYP4F2 was confirmed as the third principle genetic determinant of warfarin dos...Warfarin is a commonly used anticoagulant with a narrow therapeutic range and risk of hemorrhagic complications. After CYP2C9 and VKORC1, CYP4F2 was confirmed as the third principle genetic determinant of warfarin dose variability.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
Objective: To study the expression of activated epi-dermal growth factor receptor (EGFR) and transcrip-tion factor E2F (E2F) in Condyloma Accuminata(CA)patients. Methods: Immunofluorescent techniques were usedto inves...Objective: To study the expression of activated epi-dermal growth factor receptor (EGFR) and transcrip-tion factor E2F (E2F) in Condyloma Accuminata(CA)patients. Methods: Immunofluorescent techniques were usedto investigate the expression of activated EGFR andE2F in CA patients. Results: The expression of activated EGFR on themembrane of epithelial cells in CA lesions was sig-nificantly greater compared to expression levers inthe control group (P<0.01). Moreover, the co-expres-sion of activated EGFR and E2F was significantly in-creased compared to the control group (P<0.01). Conclusion: Our observations suggest that the in-crease in activated EGFR expression may stimulatehyperplasia in CA patients through the activation oftranscription factor E2F.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
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
Background:Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer(PCa),the long tail of cancer genes remains to be defined.Goosecoid(GSC)has been implicated ...Background:Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer(PCa),the long tail of cancer genes remains to be defined.Goosecoid(GSC)has been implicated in cancer development.However,the comprehensive biological role of GSC in pan-cancer,specifically in PCa,remains unexplored.The aim of this study was to investigate the role of GSC in PCa development.Methods:We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Omnibus,German Cancer Research Center,and our in-house cohorts.First,we evaluated the expression of GSC and its association with patient prognosis,and identified GSC-relevant genetic alterations in cancers.Further,we focused on the clinical characterization and prognostic analysis of GSC in PCa.To understand the transcriptional regulation of GSC by E2F transcription factor 1(E2F1),we performed chromatin immunoprecipitation quantitative polymerase chain reaction(qPCR).Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib.Results:GSC expression was elevated in various tumors and significantly correlated with patient prognosis.The alterations of GSC contribute to the progression of various tumors especially in PCa.Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes.Further,GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score,advanced tumor stage,lymph node metastasis,and elevated prostate-specific antigen(PSA)levels.Mechanistically,the transcription factor,E2F1,stimulates GSC by binding to its promoter region.Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment.Conclusions:GSC was highly overexpressed and strongly correlated with patient prognosis in PCa.We found that GSC,regulated by E2F1,acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.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.
基金Acknowledgements This work was supported by grants from the National Natural Science Foundation of China （No. 30971259）, and the Scientific and Technological Innovation Fund for Young Investigation, Chinese PLA General Hospital （No. 09KMM23）.
文摘Warfarin is a commonly used anticoagulant with a narrow therapeutic range and risk of hemorrhagic complications. After CYP2C9 and VKORC1, CYP4F2 was confirmed as the third principle genetic determinant of warfarin dose variability.
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Objective: To study the expression of activated epi-dermal growth factor receptor (EGFR) and transcrip-tion factor E2F (E2F) in Condyloma Accuminata(CA)patients. Methods: Immunofluorescent techniques were usedto investigate the expression of activated EGFR andE2F in CA patients. Results: The expression of activated EGFR on themembrane of epithelial cells in CA lesions was sig-nificantly greater compared to expression levers inthe control group (P<0.01). Moreover, the co-expres-sion of activated EGFR and E2F was significantly in-creased compared to the control group (P<0.01). Conclusion: Our observations suggest that the in-crease in activated EGFR expression may stimulatehyperplasia in CA patients through the activation oftranscription factor E2F.
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.
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.
基金supported by the National Natural Science Foundation of China(Nos.82173068,81974400)the Applied Basic Research Plan from Qinghai Provincial Department of Science and Technology(No.2021-ZJ-723).
文摘Background:Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer(PCa),the long tail of cancer genes remains to be defined.Goosecoid(GSC)has been implicated in cancer development.However,the comprehensive biological role of GSC in pan-cancer,specifically in PCa,remains unexplored.The aim of this study was to investigate the role of GSC in PCa development.Methods:We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Omnibus,German Cancer Research Center,and our in-house cohorts.First,we evaluated the expression of GSC and its association with patient prognosis,and identified GSC-relevant genetic alterations in cancers.Further,we focused on the clinical characterization and prognostic analysis of GSC in PCa.To understand the transcriptional regulation of GSC by E2F transcription factor 1(E2F1),we performed chromatin immunoprecipitation quantitative polymerase chain reaction(qPCR).Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib.Results:GSC expression was elevated in various tumors and significantly correlated with patient prognosis.The alterations of GSC contribute to the progression of various tumors especially in PCa.Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes.Further,GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score,advanced tumor stage,lymph node metastasis,and elevated prostate-specific antigen(PSA)levels.Mechanistically,the transcription factor,E2F1,stimulates GSC by binding to its promoter region.Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment.Conclusions:GSC was highly overexpressed and strongly correlated with patient prognosis in PCa.We found that GSC,regulated by E2F1,acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.
