CISD1,an outer mitochondrial membrane iron-sulfur cluster protein,regulates intracellular iron levels,oxidative stress,and mitochondrial dynamics,playing critical roles in cellular bioenergetics and redox homeostasis....CISD1,an outer mitochondrial membrane iron-sulfur cluster protein,regulates intracellular iron levels,oxidative stress,and mitochondrial dynamics,playing critical roles in cellular bioenergetics and redox homeostasis.Although CISD1 has been identified as a prognostic biomarker in specific cancers,its broader implications in tumorigenesis,cancer progression,and immunotherapy remain unclear.Given the heterogeneity of cancer and the need for robust biomarkers across cancers,this study conducts the first comprehensive pan-cancer analysis of CISD1 by evaluating its roles in cancer and treatment.We obtained and analyzed data from databases including TCGA,GTEx,THPA,GEPIA2.0,SangerBox,cBioPortal,TIMER2.0,CAMOIP,DAVID,SRPLOT,and TISIDB.Our findings reveal significant alterations in CISD1 expression at both transcriptional and translational levels,as well as gene mutations across multiple cancers,indicating its potential as a diagnostic biomarker and its involvement in cancer development and progression.CISD1 dysregulation is linked to poor clinical outcomes,as shown through its impact on patient prognosis.GO and KEGG analyses show that CISD1 plays critical roles in cellular bioenergetics.Notably,CISD1 expression is significantly correlated with tumor stemness indices,tumor mutation burden,microsatellite instability,and immune checkpoint proteins in multiple cancers,and altered CISD1 levels are also observed in patients responding to immunotherapy,further supporting its role not only in prognosis but also as a key predictor in immunotherapy responses and outcomes.Our findings demonstrate CISD1 as a reliable and promising diagnostic,prognostic,and immunotherapeutic biomarker for multiple cancers,emphasizing its crucial role in cancer biology and potential to guide personalized cancer therapies.展开更多
Variegation mutants are ideal model systems to study chloroplast biogenesis. We are interested in variegations whose green and whitesectored leaves arise as a consequence of the action of nuclear recessive genes. In t...Variegation mutants are ideal model systems to study chloroplast biogenesis. We are interested in variegations whose green and whitesectored leaves arise as a consequence of the action of nuclear recessive genes. In this review, we focus on the Arabidopsis var2 variegation mutant, and discuss recent progress toward understanding the function of VAR2 and the mechanism of var2-mediated variegation. VAR2 is a subunit of the chloroplast FtsH complex, which is involved in turnover of the Photosystem II reaction center D1 protein, as well as in other processes required for the development and maintenance of the photosynthetic apparatus. The cells in green sectors of var2 have normal-appearing chloroplasts whereas cells in the white sectors have abnormal plastids that lack pigments and organized lamellae. To explain the mechanism of var2 variegation, we have proposed a threshold model in which the formation of chloroplasts is due to the presence of activities/processes that are able to compensate for a lack of VAR2. To gain insight into these activities, second-site suppressor screens have been carried out to obtain mutants with nonvariegation phenotypes. Cloning and characterization of several var2 suppressor lines have uncovered several mechanisms of variegation suppression, including an unexpected link between var2 variegation and chloroplast translation.展开更多
Aim:To investigate the effects of cisplatin on the human non-small cell lung carcinoma(NCI-H460)cell line regarding cytotoxicity,genotoxicity,and expression of genes associated with apoptosis(BIRC5)and autophagy(BECN1...Aim:To investigate the effects of cisplatin on the human non-small cell lung carcinoma(NCI-H460)cell line regarding cytotoxicity,genotoxicity,and expression of genes associated with apoptosis(BIRC5)and autophagy(BECN1).Methods:Cell cultures were treated with cisplatin concentrations(0.16-33.3μmol/L)for 48 h.Mutagenicity and acute and chronic cytotoxicities were assessed using the MTT,clonogenic,and cytokinesis-block micronucleus assays.Gene expression of BIRC5 and BECN1 was evaluated by reverse transcription-polymerase chain reaction.Results:Cisplatin IC50(0.33μmol/L)increased micronucleus frequency 2.50 times.Cisplatin was also cytotoxic in the 0.6-33.3μmol/L range,with reduced expression of the BIRC5 gene,suggesting induction of apoptosis.Besides reducing the expression of the BIRC5 gene,33.3μmol/L cisplatin increased the expression of the BECN1 gene,suggesting that autophagy can be related to cisplatin resistance.Conclusion:Cisplatin inhibited NCI-H460 growth,and cisplatin IC50 induced genotoxic damage.When higher cisplatin concentrations are used,the expression of genes associated with apoptosis and autophagy was changed.This results points to a further investigation of the role of autophagy in cisplatin resistance.展开更多
文摘CISD1,an outer mitochondrial membrane iron-sulfur cluster protein,regulates intracellular iron levels,oxidative stress,and mitochondrial dynamics,playing critical roles in cellular bioenergetics and redox homeostasis.Although CISD1 has been identified as a prognostic biomarker in specific cancers,its broader implications in tumorigenesis,cancer progression,and immunotherapy remain unclear.Given the heterogeneity of cancer and the need for robust biomarkers across cancers,this study conducts the first comprehensive pan-cancer analysis of CISD1 by evaluating its roles in cancer and treatment.We obtained and analyzed data from databases including TCGA,GTEx,THPA,GEPIA2.0,SangerBox,cBioPortal,TIMER2.0,CAMOIP,DAVID,SRPLOT,and TISIDB.Our findings reveal significant alterations in CISD1 expression at both transcriptional and translational levels,as well as gene mutations across multiple cancers,indicating its potential as a diagnostic biomarker and its involvement in cancer development and progression.CISD1 dysregulation is linked to poor clinical outcomes,as shown through its impact on patient prognosis.GO and KEGG analyses show that CISD1 plays critical roles in cellular bioenergetics.Notably,CISD1 expression is significantly correlated with tumor stemness indices,tumor mutation burden,microsatellite instability,and immune checkpoint proteins in multiple cancers,and altered CISD1 levels are also observed in patients responding to immunotherapy,further supporting its role not only in prognosis but also as a key predictor in immunotherapy responses and outcomes.Our findings demonstrate CISD1 as a reliable and promising diagnostic,prognostic,and immunotherapeutic biomarker for multiple cancers,emphasizing its crucial role in cancer biology and potential to guide personalized cancer therapies.
文摘Variegation mutants are ideal model systems to study chloroplast biogenesis. We are interested in variegations whose green and whitesectored leaves arise as a consequence of the action of nuclear recessive genes. In this review, we focus on the Arabidopsis var2 variegation mutant, and discuss recent progress toward understanding the function of VAR2 and the mechanism of var2-mediated variegation. VAR2 is a subunit of the chloroplast FtsH complex, which is involved in turnover of the Photosystem II reaction center D1 protein, as well as in other processes required for the development and maintenance of the photosynthetic apparatus. The cells in green sectors of var2 have normal-appearing chloroplasts whereas cells in the white sectors have abnormal plastids that lack pigments and organized lamellae. To explain the mechanism of var2 variegation, we have proposed a threshold model in which the formation of chloroplasts is due to the presence of activities/processes that are able to compensate for a lack of VAR2. To gain insight into these activities, second-site suppressor screens have been carried out to obtain mutants with nonvariegation phenotypes. Cloning and characterization of several var2 suppressor lines have uncovered several mechanisms of variegation suppression, including an unexpected link between var2 variegation and chloroplast translation.
基金This work is supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES)(PROSUP-181/201)Fundação de AmparoàPesquisa do Estado do Rio Grande do Sul(FAPERGS).
文摘Aim:To investigate the effects of cisplatin on the human non-small cell lung carcinoma(NCI-H460)cell line regarding cytotoxicity,genotoxicity,and expression of genes associated with apoptosis(BIRC5)and autophagy(BECN1).Methods:Cell cultures were treated with cisplatin concentrations(0.16-33.3μmol/L)for 48 h.Mutagenicity and acute and chronic cytotoxicities were assessed using the MTT,clonogenic,and cytokinesis-block micronucleus assays.Gene expression of BIRC5 and BECN1 was evaluated by reverse transcription-polymerase chain reaction.Results:Cisplatin IC50(0.33μmol/L)increased micronucleus frequency 2.50 times.Cisplatin was also cytotoxic in the 0.6-33.3μmol/L range,with reduced expression of the BIRC5 gene,suggesting induction of apoptosis.Besides reducing the expression of the BIRC5 gene,33.3μmol/L cisplatin increased the expression of the BECN1 gene,suggesting that autophagy can be related to cisplatin resistance.Conclusion:Cisplatin inhibited NCI-H460 growth,and cisplatin IC50 induced genotoxic damage.When higher cisplatin concentrations are used,the expression of genes associated with apoptosis and autophagy was changed.This results points to a further investigation of the role of autophagy in cisplatin resistance.
