Background:Prostate adenocarcinoma(PRAD)is one of the most commonly diagnosed cancers in men.Expanding evidence suggests a significant association between cancer progression and RNA modifications.However,our knowledge...Background:Prostate adenocarcinoma(PRAD)is one of the most commonly diagnosed cancers in men.Expanding evidence suggests a significant association between cancer progression and RNA modifications.However,our knowledge of the link between m^(5)C and hm^(5)C pathways with PRAD is limited.Therefore,we aimed to explore the diagnostic and prognostic values of m^(5)C and hm^(5)C regulators in PRAD.Methods:In this study,genetic alterations in m^(5)C and hm^(5)C regulators were identified using publicly available databases.Expression levels of regulators in PRAD samples were retrieved via the RTCGA package in the R environment.Differentially expressed genes in these pathways between tumor and non-tumor samples were identified using the R‘limma’package.Correlation among m^(5)C and hm^(5)C pathway members was examined employing the‘Hmisc’package in R.We utilized the‘survminer’package in R for applying the Kaplan-Meier method to estimate the overall survival rate of m^(5)C and hm^(5)C regulators.The discrimination power of selected regulators between tumor and non-tumor samples was analyzed by the receiver operating characteristic curve.Furthermore,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were carried out to enrich the affected biological processes and pathways.Results:Differentially expressed genes in these pathways between tumor and non-tumor samples,correlation among m^(5)C and hm^(5)C pathway members,and prognostic value of the regulators were evaluated.Obtained results unveiled the mRNA level differences as the key genetic alterations for m^(5)C and hm^(5)C regulators between tumor and non-tumor samples.UHRF1,TET3,and NEIL1 were significantly upregulated in tumor samples,whereas MECP2 and EGR1 were significantly downregulated for m^(5)C and hm^(5)C regulators.UHRF1,DNMT1,NSUN2,NSUN4,C1orf77,C3orf37,WDR77,NEIL1,and TDG genes were identified as candidate prognostic markers of overall survival.The upregulated genes in patient samples with genetic alterations in m^(5)C and hm^(5)C pathways enriched cell cycle-related processes.Conclusion:In summary,our findings suggest that the m^(5)C and hm^(5)C regulators might play a role in PRAD development by activation of proliferation,and the UHRF1,NSUN2,and NEIL1 genes have the potential to be utilized as clinical biomarkers.Established correlative relationships require experimental validation through functional studies in prostate cancer cell lines.展开更多
2015年4月21日上午,在泰勒霍普森CIMT2015的展台上,本刊记者又见到了老朋友——泰勒霍普森中国区总经理曾理先生,同时,他还为本刊记者介绍了一位新朋友——Neil B Curtis先生,泰勒霍普森销售总监。曾总风采依旧,欢笑更胜。坐下细聊方知...2015年4月21日上午,在泰勒霍普森CIMT2015的展台上,本刊记者又见到了老朋友——泰勒霍普森中国区总经理曾理先生,同时,他还为本刊记者介绍了一位新朋友——Neil B Curtis先生,泰勒霍普森销售总监。曾总风采依旧,欢笑更胜。坐下细聊方知,＂喜＂出有因。展开更多
Objective:To explore the genetic changes in the progression of castration-resistant prostate cancer(CRPC)and neuroendocrine prostate cancer(NEPC)and the reason why these cancers resist existing therapies.Methods:We em...Objective:To explore the genetic changes in the progression of castration-resistant prostate cancer(CRPC)and neuroendocrine prostate cancer(NEPC)and the reason why these cancers resist existing therapies.Methods:We employed our CRPC cell line microarray and other CRPC or NEPC datasets to screen the target gene NEIL3.Lentiviral transfection and RNA interference were used to construct overexpression and knockdown cell lines.Cell and animal models of radiotherapy were established by using a medical electron linear accelerator.Flow cytometry was used to detect apoptosis or cell cycle progression.Western blot and qPCR were used to detect changes in the protein and RNA levels.Results:TCGA and clinical patient datasets indicated that NEIL3 was downregulated in CRPC and NEPC cell lines,and NEIL3 was correlated with a high Gleason score but a good prognosis.Further functional studies demonstrated that NEIL3 had no effect on the proliferation and migration of PCa cells.However,cell and animal radiotherapy models revealed that NEIL3 could facilitate the radiotherapy sensitivity of PCa cells,while loss of NEIL3 activated radiotherapy resistance.Mechanistically,we found that NEIL3 negatively regulated the expression of ATR,and higher NEIL3 expression repressed the ATR/CHK1 pathway,thus regulating the cell cycle.Conclusions:We demonstrated that NEIL3 may serve as a diagnostic or therapeutic target for therapy-resistant patients.展开更多
AIM:To identify genetic polymorphisms in the promoter region of the human base excision repair gene NEIL1 in gastric cancer patients.METHODS:The NEIL1 promoter region in DNA from 80 Japanese patients with gastric canc...AIM:To identify genetic polymorphisms in the promoter region of the human base excision repair gene NEIL1 in gastric cancer patients.METHODS:The NEIL1 promoter region in DNA from 80 Japanese patients with gastric cancer was searched for genetic polymorphisms by polymerase chain reaction-single-strand conformation polymorphism and subsequent sequencing analyses.RESULTS:Three novel genetic polymorphisms,i.e.c.-3769C>T,c.-3170T>G,and c.-2681TA[8],were identified in the NEIL1 promoter region at an allele frequency of 0.6%,9.4%,and 4.4%,respectively,in Japanese gastric cancer patients.CONCLUSION:Three NEIL1 promoter polymorphisms detected in this study may be of importance in gastric carcinogenesis.展开更多
基金Health Institutes of Turkey(TUSEBProject No.TA01-4213)for the financial support of the present study.
文摘Background:Prostate adenocarcinoma(PRAD)is one of the most commonly diagnosed cancers in men.Expanding evidence suggests a significant association between cancer progression and RNA modifications.However,our knowledge of the link between m^(5)C and hm^(5)C pathways with PRAD is limited.Therefore,we aimed to explore the diagnostic and prognostic values of m^(5)C and hm^(5)C regulators in PRAD.Methods:In this study,genetic alterations in m^(5)C and hm^(5)C regulators were identified using publicly available databases.Expression levels of regulators in PRAD samples were retrieved via the RTCGA package in the R environment.Differentially expressed genes in these pathways between tumor and non-tumor samples were identified using the R‘limma’package.Correlation among m^(5)C and hm^(5)C pathway members was examined employing the‘Hmisc’package in R.We utilized the‘survminer’package in R for applying the Kaplan-Meier method to estimate the overall survival rate of m^(5)C and hm^(5)C regulators.The discrimination power of selected regulators between tumor and non-tumor samples was analyzed by the receiver operating characteristic curve.Furthermore,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were carried out to enrich the affected biological processes and pathways.Results:Differentially expressed genes in these pathways between tumor and non-tumor samples,correlation among m^(5)C and hm^(5)C pathway members,and prognostic value of the regulators were evaluated.Obtained results unveiled the mRNA level differences as the key genetic alterations for m^(5)C and hm^(5)C regulators between tumor and non-tumor samples.UHRF1,TET3,and NEIL1 were significantly upregulated in tumor samples,whereas MECP2 and EGR1 were significantly downregulated for m^(5)C and hm^(5)C regulators.UHRF1,DNMT1,NSUN2,NSUN4,C1orf77,C3orf37,WDR77,NEIL1,and TDG genes were identified as candidate prognostic markers of overall survival.The upregulated genes in patient samples with genetic alterations in m^(5)C and hm^(5)C pathways enriched cell cycle-related processes.Conclusion:In summary,our findings suggest that the m^(5)C and hm^(5)C regulators might play a role in PRAD development by activation of proliferation,and the UHRF1,NSUN2,and NEIL1 genes have the potential to be utilized as clinical biomarkers.Established correlative relationships require experimental validation through functional studies in prostate cancer cell lines.
基金supported by the National Natural Science Foundation of China(Grant Nos.81672550 and 81974395)Guangdong Basic and Applied Basic Research Foundation(Grant No.2019A1515011437)+4 种基金Guangzhou Science and Technology Cooperation Program(Foreign Research and Development Cooperation)(Grant No.201807010087)Clinical Research 5010 Program of Sun Yat-sen University(Grant No.2019005)Sun Yat-Sen Clinical Research and Cultivation Project of Sun Yat Sen University(Grant No.201702)to Hai Huangsupported by the National Natural Science Foundation of China(Grant No.81702527)supported by the China Scholarship Council(Grant No.201906380075).
文摘Objective:To explore the genetic changes in the progression of castration-resistant prostate cancer(CRPC)and neuroendocrine prostate cancer(NEPC)and the reason why these cancers resist existing therapies.Methods:We employed our CRPC cell line microarray and other CRPC or NEPC datasets to screen the target gene NEIL3.Lentiviral transfection and RNA interference were used to construct overexpression and knockdown cell lines.Cell and animal models of radiotherapy were established by using a medical electron linear accelerator.Flow cytometry was used to detect apoptosis or cell cycle progression.Western blot and qPCR were used to detect changes in the protein and RNA levels.Results:TCGA and clinical patient datasets indicated that NEIL3 was downregulated in CRPC and NEPC cell lines,and NEIL3 was correlated with a high Gleason score but a good prognosis.Further functional studies demonstrated that NEIL3 had no effect on the proliferation and migration of PCa cells.However,cell and animal radiotherapy models revealed that NEIL3 could facilitate the radiotherapy sensitivity of PCa cells,while loss of NEIL3 activated radiotherapy resistance.Mechanistically,we found that NEIL3 negatively regulated the expression of ATR,and higher NEIL3 expression repressed the ATR/CHK1 pathway,thus regulating the cell cycle.Conclusions:We demonstrated that NEIL3 may serve as a diagnostic or therapeutic target for therapy-resistant patients.
基金Supported by Grants-in-Aid from Ministry of Health, Labour and Welfare for the Comprehensive 10-Year Strategy for Cancer Control (19-19)Japan Society for the Promotion of Science for Scientific Research, No. 19790286+1 种基金Ministry of Education, Culture,Sports, Science and Technology for priority area, No. 20014007the 21st century COE program
文摘AIM:To identify genetic polymorphisms in the promoter region of the human base excision repair gene NEIL1 in gastric cancer patients.METHODS:The NEIL1 promoter region in DNA from 80 Japanese patients with gastric cancer was searched for genetic polymorphisms by polymerase chain reaction-single-strand conformation polymorphism and subsequent sequencing analyses.RESULTS:Three novel genetic polymorphisms,i.e.c.-3769C>T,c.-3170T>G,and c.-2681TA[8],were identified in the NEIL1 promoter region at an allele frequency of 0.6%,9.4%,and 4.4%,respectively,in Japanese gastric cancer patients.CONCLUSION:Three NEIL1 promoter polymorphisms detected in this study may be of importance in gastric carcinogenesis.
