There is mounting evidence that targeting mitochondrial dysfunction following neurotrauma could be key in developing effective therapeutic strategies since mitochondria are known to play a major role in cellular bioen...There is mounting evidence that targeting mitochondrial dysfunction following neurotrauma could be key in developing effective therapeutic strategies since mitochondria are known to play a major role in cellular bioenergetics, function, and survival following traumatic spinal cord injury （SCI） （Rabchevsky et al., 2011）. Our research group is one of the pioneers in targeting mitochondrial dysfunction to foster functional neuroprotection, having documented that phar- macological maintenance of mitochondrial function acutely results in long-term neuroprotection and improved function- al recover. We have recently reported that treatment with the pleiotropic drug, pioglitazone, maintains acute mitochondrial integrity correlated with chronic tissue sparing and functional recovery after contusion SCI, but that this was not correlated with altered neuroinflammation （Patel et al., 2017）. We herein propose that the mechanism（s） by which pioglitazone confers neuroprotection may not be entirely dependent upon its activation of peroxisome proliferator activated receptor （PPAR）,展开更多
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
基金funded by NIH R21NS096670(AGR)Craig H.Neilsen Foundation 476719(AGR)+3 种基金Kentucky Spinal Cord and Head Injury Research Trust#15-14A(PGS)Veterans Affairs Merit Review Award#I01BX003405(PGS)University of Kentucky Spinal Cord and Brain Injury Center Chair Endowments(AGR&PGS)NIH/NINDS 2P30NS051220
文摘There is mounting evidence that targeting mitochondrial dysfunction following neurotrauma could be key in developing effective therapeutic strategies since mitochondria are known to play a major role in cellular bioenergetics, function, and survival following traumatic spinal cord injury （SCI） （Rabchevsky et al., 2011）. Our research group is one of the pioneers in targeting mitochondrial dysfunction to foster functional neuroprotection, having documented that phar- macological maintenance of mitochondrial function acutely results in long-term neuroprotection and improved function- al recover. We have recently reported that treatment with the pleiotropic drug, pioglitazone, maintains acute mitochondrial integrity correlated with chronic tissue sparing and functional recovery after contusion SCI, but that this was not correlated with altered neuroinflammation （Patel et al., 2017）. We herein propose that the mechanism（s） by which pioglitazone confers neuroprotection may not be entirely dependent upon its activation of peroxisome proliferator activated receptor （PPAR）,
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.
