The effects of steroid hormones are believed to be mediated by their nuclear receptors(NRs).The p160 coactivator family,including steroid receptor coactivator-1(SRC-1),2 and 3,has been shown to physically interact wit...The effects of steroid hormones are believed to be mediated by their nuclear receptors(NRs).The p160 coactivator family,including steroid receptor coactivator-1(SRC-1),2 and 3,has been shown to physically interact with NRs to enhance their transactivational activities.Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord.It is not only localized in neurons but also detectable in neuroglial cells(mainly localized in the nuclei but also detectable in the extra-nuclear components).Although the expression of SRC-1 is regulated by many steroids,it is also regulated by some non-steroidal factors such as injury,sound and light.Functionally,SRC-1 has been implied in normal function such as development and ageing,learning and memory,central regulation on reproductive behaviors,motor and food intake.Pathologically,SRC-1 may play a role in the regulation of neuropsychiatric disorders(including stress,depression,anxiety,and autism spectrum disorder),metabolite homeostasis and obesity as well as tumorigenesis.Under most conditions,the related mechanisms are far from elucidation;although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity.Several inhibitors and stimulator of SRC-1 have shown anti-cancer potentials,but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear.Therefore,to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.展开更多
Circular RNAs(circRNAs)are RNAs with a special closed loop structure,which play important roles in tumors and other diseases.Due to the time consumption of biological experiments,computational methods for predicting a...Circular RNAs(circRNAs)are RNAs with a special closed loop structure,which play important roles in tumors and other diseases.Due to the time consumption of biological experiments,computational methods for predicting associations between circRNAs and diseases become a better choice.Taking the limited number of verified circRNA-disease associations into account,we propose a method named CDWBMS,which integrates a small number of verified circRNA-disease associations with a plenty of circRNA information to discover the novel circRNA-disease associations.CDWBMS adopts an improved weighted biased meta-structure search algorithm on a heterogeneous network to predict associations between circRNAs and diseases.In terms of leave-one-out-cross-validation(LOOCV),10-fold cross-validation and 5-fold cross-validation,CDWBMS yields the area under the receiver operating characteristic curve(AUC)values of 0.9216,0.9172 and 0.9005,respectively.Furthermore,case studies show that CDWBMS can predict unknow circRNA-disease associations.In conclusion,CDWBMS is an effective method for exploring disease-related circRNAs.展开更多
基金supported by the National Science Foundation of China(NSFC,No.81571059)the Postdoctoral Research Foundation of China(No.2019M653976)Natural Science Foundation of Chongqing,China(No.cstc2019jcyj-msxmX0255).
文摘The effects of steroid hormones are believed to be mediated by their nuclear receptors(NRs).The p160 coactivator family,including steroid receptor coactivator-1(SRC-1),2 and 3,has been shown to physically interact with NRs to enhance their transactivational activities.Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord.It is not only localized in neurons but also detectable in neuroglial cells(mainly localized in the nuclei but also detectable in the extra-nuclear components).Although the expression of SRC-1 is regulated by many steroids,it is also regulated by some non-steroidal factors such as injury,sound and light.Functionally,SRC-1 has been implied in normal function such as development and ageing,learning and memory,central regulation on reproductive behaviors,motor and food intake.Pathologically,SRC-1 may play a role in the regulation of neuropsychiatric disorders(including stress,depression,anxiety,and autism spectrum disorder),metabolite homeostasis and obesity as well as tumorigenesis.Under most conditions,the related mechanisms are far from elucidation;although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity.Several inhibitors and stimulator of SRC-1 have shown anti-cancer potentials,but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear.Therefore,to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.
基金The work was supported by the National Natural Science Foundation of China under Grant Nos.61972451,61672334 and 61902230the Fundamental Research Funds for the Central Universities of China under Grant No.GK201901010.
文摘Circular RNAs(circRNAs)are RNAs with a special closed loop structure,which play important roles in tumors and other diseases.Due to the time consumption of biological experiments,computational methods for predicting associations between circRNAs and diseases become a better choice.Taking the limited number of verified circRNA-disease associations into account,we propose a method named CDWBMS,which integrates a small number of verified circRNA-disease associations with a plenty of circRNA information to discover the novel circRNA-disease associations.CDWBMS adopts an improved weighted biased meta-structure search algorithm on a heterogeneous network to predict associations between circRNAs and diseases.In terms of leave-one-out-cross-validation(LOOCV),10-fold cross-validation and 5-fold cross-validation,CDWBMS yields the area under the receiver operating characteristic curve(AUC)values of 0.9216,0.9172 and 0.9005,respectively.Furthermore,case studies show that CDWBMS can predict unknow circRNA-disease associations.In conclusion,CDWBMS is an effective method for exploring disease-related circRNAs.
