Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic valu...Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.展开更多
Background:Temozolomide(TMZ)resistance is a significant challenge in treating glioblastoma(GBM).Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers.This study aimed to in...Background:Temozolomide(TMZ)resistance is a significant challenge in treating glioblastoma(GBM).Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers.This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.Methods:Key extracellular matrix components,including collagens,were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models.Human GBM cell lines(U251,TS667)and mouse primary GBM cells were used for in vitro studies.RNA-sequencing analysis,chromatin immunoprecipitation,immunoprecipitation-mass spectrometry,and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation.A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1(P4HA1)and yes-associated protein(YAP)in sensitizing GBM cells to TMZ.Results:This study revealed that TMZ exposure significantly elevated collagen type I(COL I)expression in both GBM patients and murine models.Collagen accumulation sustained GBM cell survival under TMZ-induced stress,contributing to enhanced TMZ resistance.Mechanistically,P4HA1 directly binded to and hydroxylated YAP,preventing ubiquitination-mediated YAP degradation.Stabilized YAP robustly drove collagen type I alpha 1(COL1A1)transcription,leading to increased collagen deposition.Disruption of the P4HA1-YAP axis effectively reduced COL I deposition,sensitized GBM cells to TMZ,and significantly improved mouse survival.Conclusion:P4HA1 maintained YAP-mediated COL1A1 transcription,leading to collagen accumulation and promoting chemoresistance in GBM.展开更多
Owing to the complexities associated with the central nervous system,establishing research and evaluation models has posed challenges in the field of brain tumor research.This has significantly hindered the developmen...Owing to the complexities associated with the central nervous system,establishing research and evaluation models has posed challenges in the field of brain tumor research.This has significantly hindered the development of treatments for brain tumors.1 To enable our understanding of the complex interplay between neoplastic cells and their microenvironment,and to achieve significant advances in brain tumor research,three recent publications in the Special Issue"Advances in understanding brain tumor and perspective for clinical&translational research"of the journal concentrate on elucidating the diagnostic modalities and refining cellular and animal models.2,3,4 These contributions provide diverse avenues for investigating brain tumors and cerebral metastases.展开更多
Purpose:Three-way decision(3WD)and probabilistic rough sets(PRSs)are theoretical tools capable of simulating humans’multi-level and multi-perspective thinking modes in the field of decision-making.They are proposed t...Purpose:Three-way decision(3WD)and probabilistic rough sets(PRSs)are theoretical tools capable of simulating humans’multi-level and multi-perspective thinking modes in the field of decision-making.They are proposed to assist decision-makers in better managing incomplete or imprecise information under conditions of uncertainty or fuzziness.However,it is easy to cause decision losses and the personal thresholds of decision-makers cannot be taken into account.To solve this problem,this paper combines picture fuzzy(PF)multi-granularity(MG)with 3WD and establishes the notion of PF MG 3WD.Design/methodology/approach:An effective incomplete model based on PF MG 3WD is designed in this paper.First,the form of PF MG incomplete information systems(IISs)is established to reasonably record the uncertain information.On this basis,the PF conditional probability is established by using PF similarity relations,and the concept of adjustable PF MG PRSs is proposed by using the PF conditional probability to fuse data.Then,a comprehensive PF multi-attribute group decision-making(MAGDM)scheme is formed by the adjustable PF MG PRSs and the VlseKriterijumska Optimizacija I Kompromisno Resenje(VIKOR)method.Finally,an actual breast cancer data set is used to reveal the validity of the constructed method.Findings:The experimental results confirm the effectiveness of PF MG 3WD in predicting breast cancer.Compared with existing models,PF MG 3WD has better robustness and generalization performance.This is mainly due to the incomplete PF MG 3WD proposed in this paper,which effectively reduces the influence of unreasonable outliers and threshold settings.Originality/value:The model employs the VIKOR method for optimal granularity selections,which takes into account both group utility maximization and individual regret minimization,while incorporating decision-makers’subjective preferences as well.This ensures that the experiment maintains higher exclusion stability and reliability,enhancing the robustness of the decision results.展开更多
基金supported by the Nature Science Foundation of Chongqing(Nos.cstc2016jcyjA0838 and cstc2020jcyj-msxmX0376).
文摘Background:PLK3,which played an important role in cell cycle progression and stress response,was identified as highly expressed in various carcinomas.However,the functions,molecular characteristics,and prognostic value of PLK3 in glioma remained unexplored.Methods:We analyzed PLK3 expression in glioma samples from multiple databases.Both overexpression and knockdown of Plk3 were performed to investigate tumor cell growth in glioma,and the transplanted glioma mouse model demonstrated the role of Plk3 on tumor progression.Immunohistochemistry was conducted to detect PLK3 expression and immune cell infiltration.The trans-well assay for PLK3 on the immune cells recruitment was also determined.Additionally,we further evaluated the correlation between PLK3 and PD-1/PD-L1 as well as other immune checkpoints.Results:We found that an increased level of PLK3 was associated with malignancy and poor prognosis of glioma,and further validated that PLK3 promoted glioma progression.PLK3 also played a crucial role in immune response and was involved in Tcell immune suppression.Specifically,we revealed that CD8^(+)and CD4^(+)Tcell infiltration was decreased in Plk3 overexpressed xenografts.Furthermore,it was predicted that PLK3 was synergistic with other checkpoint members in glioma.In general,high expression of PLK3 was associated with a malignant process and poor prognosis in glioma patients.Conclusion:Our findings indicated that PLK3 expression level was highly correlated to the malignancy of gliomas,and we validated that PLK3 could promote the GBM progress in vitro and in vivo.Furthermore,PLK3 played important roles in Tcell and neutrophil immune response in glioma.Besides,the conspicuous association between PLK3 and other immune checkpoints was also observed.Crucially,high-level PLK3 expression was revealed to be related to poor clinical prognosis.These results demonstrated that PLK3 may serve as a prognostic biomarker and a potential target for glioma.
基金supported by grants from the National Natural Science Foundation of China(Nos.82072799 and 82103494)Natural Science Foundation of Chongqing(Nos.CSTB2022NSCQ-MSX0843 and cstc2020jcyjmsxmX0376)+1 种基金Scientific and Technological Research Program of Chongqing Municipal Education Commission(Nos.KJZD-K202200410 and KJQN202300434)CQMU Program for Youth Innovation in Future Medicine(No.W0106).
文摘Background:Temozolomide(TMZ)resistance is a significant challenge in treating glioblastoma(GBM).Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers.This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.Methods:Key extracellular matrix components,including collagens,were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models.Human GBM cell lines(U251,TS667)and mouse primary GBM cells were used for in vitro studies.RNA-sequencing analysis,chromatin immunoprecipitation,immunoprecipitation-mass spectrometry,and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation.A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1(P4HA1)and yes-associated protein(YAP)in sensitizing GBM cells to TMZ.Results:This study revealed that TMZ exposure significantly elevated collagen type I(COL I)expression in both GBM patients and murine models.Collagen accumulation sustained GBM cell survival under TMZ-induced stress,contributing to enhanced TMZ resistance.Mechanistically,P4HA1 directly binded to and hydroxylated YAP,preventing ubiquitination-mediated YAP degradation.Stabilized YAP robustly drove collagen type I alpha 1(COL1A1)transcription,leading to increased collagen deposition.Disruption of the P4HA1-YAP axis effectively reduced COL I deposition,sensitized GBM cells to TMZ,and significantly improved mouse survival.Conclusion:P4HA1 maintained YAP-mediated COL1A1 transcription,leading to collagen accumulation and promoting chemoresistance in GBM.
文摘Owing to the complexities associated with the central nervous system,establishing research and evaluation models has posed challenges in the field of brain tumor research.This has significantly hindered the development of treatments for brain tumors.1 To enable our understanding of the complex interplay between neoplastic cells and their microenvironment,and to achieve significant advances in brain tumor research,three recent publications in the Special Issue"Advances in understanding brain tumor and perspective for clinical&translational research"of the journal concentrate on elucidating the diagnostic modalities and refining cellular and animal models.2,3,4 These contributions provide diverse avenues for investigating brain tumors and cerebral metastases.
基金funded by the National Natural Science Foundation of China(Nos:62272284,61972238 and 62072294)the Special Fund for Science and Technology Innovation Teams of Shanxi Province(No:202204051001015)the Cultivate Scientific Research Excellence Programs of Higher Education Institutions in Shanxi(CSREP)(No:2019SK036)。
文摘Purpose:Three-way decision(3WD)and probabilistic rough sets(PRSs)are theoretical tools capable of simulating humans’multi-level and multi-perspective thinking modes in the field of decision-making.They are proposed to assist decision-makers in better managing incomplete or imprecise information under conditions of uncertainty or fuzziness.However,it is easy to cause decision losses and the personal thresholds of decision-makers cannot be taken into account.To solve this problem,this paper combines picture fuzzy(PF)multi-granularity(MG)with 3WD and establishes the notion of PF MG 3WD.Design/methodology/approach:An effective incomplete model based on PF MG 3WD is designed in this paper.First,the form of PF MG incomplete information systems(IISs)is established to reasonably record the uncertain information.On this basis,the PF conditional probability is established by using PF similarity relations,and the concept of adjustable PF MG PRSs is proposed by using the PF conditional probability to fuse data.Then,a comprehensive PF multi-attribute group decision-making(MAGDM)scheme is formed by the adjustable PF MG PRSs and the VlseKriterijumska Optimizacija I Kompromisno Resenje(VIKOR)method.Finally,an actual breast cancer data set is used to reveal the validity of the constructed method.Findings:The experimental results confirm the effectiveness of PF MG 3WD in predicting breast cancer.Compared with existing models,PF MG 3WD has better robustness and generalization performance.This is mainly due to the incomplete PF MG 3WD proposed in this paper,which effectively reduces the influence of unreasonable outliers and threshold settings.Originality/value:The model employs the VIKOR method for optimal granularity selections,which takes into account both group utility maximization and individual regret minimization,while incorporating decision-makers’subjective preferences as well.This ensures that the experiment maintains higher exclusion stability and reliability,enhancing the robustness of the decision results.
