Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods...Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.展开更多
Columbianetin acetate(CE)is one of the effective components of Angelica pubescens.So far,the specific role and molecular mechanism of CE in pancreatic cancer are not clear.Thus,this study aimed to explore the specific...Columbianetin acetate(CE)is one of the effective components of Angelica pubescens.So far,the specific role and molecular mechanism of CE in pancreatic cancer are not clear.Thus,this study aimed to explore the specific mechanism of CE on pancreatic cancer.The target genes combined with CE were predicted through the PharmMapper database and the 3D molecular structure of CE.Then,the Cancer Genome Atlas(TCGA)and Cistrome data browser(DB)databases were used to screen Meiotic nuclear divisions 1(MND1)-related genes,transcription factors,and transcription factor data sets,and the intersection of the above data sets.The“limma”package in the R and gene expression profiling interactive analysis(GEPIA)databases were used to analyze the correlation and survival difference between the target genes and MND1 to predict the degree of association between CE and MND1.Western blotting and RT-PCR experiments revealed the regulatory relationship among CE,E2F1,and MND1 at the cellular level.The specific effects of CE on pancreatic cancer cells were explored through CCK8,wound healing,migration,and flow cycle experiments.E2F1,also the predictive transcription factor of MND1,was also the predictive target protein of CE.At the same time,E2F1 and MND1 were closely related in pancreatic tissue.In the cell function experiment,CE and interference with E2F1 expression could reduce the gene and protein expression of MND1,which was closely associated with cell proliferation,migration,and cycle development.Similarly,interfering with the expression of mnd1 can also inhibit the further development of tumor cells.CE may inhibit the development of pancreatic cancer cells by reducing the expression of MND1.This implies that CE may be a potential novel agent for the treatment of pancreatic cancer.展开更多
Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet cl...Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need.In this study,we tested the anticancer activity of orlistat,an FDA-approved anti-obesity drug,in human and mouse cancer cells in vitro and in vivo,and we found that orlistat,as a single agent,inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro.Mechanistically,we found that orlistat reduced the expression of GPX4,a central ferroptosis regulator,and induced lipid peroxidation.In addition,we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2,a molecule regulating the lipid droplet homeostasis,as a novel target of orlistat.Moreover,in a mouse xenograft model,orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control(P<0.05).Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.展开更多
基金supported by grants from National Innovation Program for College Students(202210367076)Graduate Student Research Innovation Program of Bengbu Medical College(Byycxz22016)the National Natural Science Foundation of China(82072585),and the Key Research Project of Bengbu Medical College(No.2020byzd029).
文摘Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality rate.Currently,prevention and effective treatment are urgent issues that need to be addressed.Methods:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival analysis.Simultaneously,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of PC.The small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell lines.Results:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell proliferation.Wound healing and Transwell assays revealed that MND1 knockdown reduced cell migration and invasion.Flow cytometry revealed that inhibiting MND1 hindered the cell cycle.Furthermore,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of MND1.Notably,MND1 had a positive effect on H2AFX expression in PC cells.Elevated MND1 expression suggests the low overall survival rate of individuals diagnosed with PC.Conclusion:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.
基金supported by grants from the Key Natural Science Project of Anhui Provincial Education Department(Nos.KJ2018A0221,KJ2020A0578 and KJ2021A0773)National Innovation Program for College Students(No.202010367046)Anhui Provincial Undergraduate Innovative Training Program(Nos.S202010367008,S202110367030 and S202110367112).
文摘Columbianetin acetate(CE)is one of the effective components of Angelica pubescens.So far,the specific role and molecular mechanism of CE in pancreatic cancer are not clear.Thus,this study aimed to explore the specific mechanism of CE on pancreatic cancer.The target genes combined with CE were predicted through the PharmMapper database and the 3D molecular structure of CE.Then,the Cancer Genome Atlas(TCGA)and Cistrome data browser(DB)databases were used to screen Meiotic nuclear divisions 1(MND1)-related genes,transcription factors,and transcription factor data sets,and the intersection of the above data sets.The“limma”package in the R and gene expression profiling interactive analysis(GEPIA)databases were used to analyze the correlation and survival difference between the target genes and MND1 to predict the degree of association between CE and MND1.Western blotting and RT-PCR experiments revealed the regulatory relationship among CE,E2F1,and MND1 at the cellular level.The specific effects of CE on pancreatic cancer cells were explored through CCK8,wound healing,migration,and flow cycle experiments.E2F1,also the predictive transcription factor of MND1,was also the predictive target protein of CE.At the same time,E2F1 and MND1 were closely related in pancreatic tissue.In the cell function experiment,CE and interference with E2F1 expression could reduce the gene and protein expression of MND1,which was closely associated with cell proliferation,migration,and cycle development.Similarly,interfering with the expression of mnd1 can also inhibit the further development of tumor cells.CE may inhibit the development of pancreatic cancer cells by reducing the expression of MND1.This implies that CE may be a potential novel agent for the treatment of pancreatic cancer.
基金supported by grants from the National Natural Science Foundation of China(No.81672314)the Key Natural Science Project of Anhui Provincial Education Department(No.KJ2020A1244,KJ2020A0578,and KJ2018A0221)National Innovation Program for College Students(Nos.201810367021 and 201710367036).
文摘Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers,including lung cancer;however,targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need.In this study,we tested the anticancer activity of orlistat,an FDA-approved anti-obesity drug,in human and mouse cancer cells in vitro and in vivo,and we found that orlistat,as a single agent,inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro.Mechanistically,we found that orlistat reduced the expression of GPX4,a central ferroptosis regulator,and induced lipid peroxidation.In addition,we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2,a molecule regulating the lipid droplet homeostasis,as a novel target of orlistat.Moreover,in a mouse xenograft model,orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control(P<0.05).Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
