Recently,Richter et al.[1]revealed the potential functions of the interaction between the serine/threonine kinase Tank-binding kinase 1（TBK1）and the autophagy receptor optineurin（OPTN）.The TBK1-OPTN axis targets d...Recently,Richter et al.[1]revealed the potential functions of the interaction between the serine/threonine kinase Tank-binding kinase 1（TBK1）and the autophagy receptor optineurin（OPTN）.The TBK1-OPTN axis targets damaged mitochondria for degradation via PINK1/parkin-mediated mitophagy[2,3].Indeed,TBK1 can phosphorylate OPTN at Ser177,Ser473,or Ser513 to enhance the binding capacity of OPTN with poly-ubiquitin（poly-UB）chains.Conversely,展开更多
Recently, Khayachi et al.;showed that fragile X mental retardation protein （FMRP） is an active substrate of the small ubiquitin-like modifier （SUMO） pathway in neurons.FMRP SUMOylation is induced by the activation...Recently, Khayachi et al.;showed that fragile X mental retardation protein （FMRP） is an active substrate of the small ubiquitin-like modifier （SUMO） pathway in neurons.FMRP SUMOylation is induced by the activation of metabotropic glutamate receptors （mGlu5Rs）. FMRP展开更多
Bacterial small RNAs （sRNAs） are an emerging class of regulatory RNAs of about 40-500 nucleotides in length and, by binding to their target mRNAs or proteins, get involved in many biological processes such as sensin...Bacterial small RNAs （sRNAs） are an emerging class of regulatory RNAs of about 40-500 nucleotides in length and, by binding to their target mRNAs or proteins, get involved in many biological processes such as sensing environmental changes and regulating gene expres- sion. Thus, identification of bacterial sRNAs and their targets has become an important part of sRNA biology. Current strategies for discovery of sRNAs and their targets usually involve bioinformatics prediction followed by experimental validation, emphasizing a key role for bioinformatics prediction. Here, therefore, we provided an overview on prediction methods, focusing on the merits and limita- tions of each class of models. Finally, we will present our thinking on developing related bioinformafics models in future.展开更多
To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can l...To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can lead to declines in diastolic and systolic functions and eventually develop heart failure.Angiotensin II(Ang II)can mediate cardiac hypertrophy through the angiotensin II type 1 receptor(AT1R).^([1])展开更多
Interleukin-27(IL-27),a heterodimeric cytokine,plays a protective role in diabetes.Ghrelin,a gastric hormone,provides a hunger signal to the central nervous system to stimulate food intake.The relationship between IL-...Interleukin-27(IL-27),a heterodimeric cytokine,plays a protective role in diabetes.Ghrelin,a gastric hormone,provides a hunger signal to the central nervous system to stimulate food intake.The relationship between IL-27 and ghrelin is still unexplored.Here we investigated that signal transducer and activator of transcription 3(STAT3)—mechanistic target of rapamycin(mTOR)signaling mediates the suppression of ghrelin induced by IL-27.Co-localization of interleukin 27 receptor subunit alpha(WSX-1)and ghrelin was observed in mouse and human gastric mucosa.Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57 BL/6 J mice and high-fat diet-induced-obese mice.IL-27 inhibited the production of ghrelin in mHypoE-N42 cells.Inhibition of mTOR activity induced by mTOR siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells.Stat 3 siRNA also abolished the inhibitory effect of IL-27 on ghrelin.IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells.In conclusion,IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.展开更多
Background S-Phase kinase associated protein 2(SKP2)is a key regulator of the cell cycle and proliferation linked to cancer development.Our recent study has revealed that knocking out Skp2 in a mouse model significant...Background S-Phase kinase associated protein 2(SKP2)is a key regulator of the cell cycle and proliferation linked to cancer development.Our recent study has revealed that knocking out Skp2 in a mouse model significantly activates anti-tumor immunity.Although several studies have examined SKP2 in relation to the tumor immune microenvironment using public datasets,a comprehensive pan-cancer evaluation that integrates multi-omics layers and in vivo validation has remained limited.Methods In this study,we integrated multi-omics data from diverse public datasets to comprehensively analyze SKP2 expression characteristics and its relationship to tumor immunity across pan-cancer.A multiplex immunofluorescence assay was performed on tumors from Skp2 knockout and Skp2-intact mouse models for validation.Results Our findings indicate that SKP2 is overexpressed in various cancer types,leading to poor prognosis.Single-cell transcriptomic analyses further revealed that SKP2 is predominantly expressed in malignant and immune cells.Notably,a multiplex immunofluorescence assay on tumors from Skp2 knockout and Skp2-intact mouse models and pan-cancer data unveiled a correlation between SKP2 and the“immune-cold”microenvironment,which,possibly linked to the weakened antigen presentation,reduced secretion of chemokines in SKP2-overexpressing cancers.Additionally,we observed that SKP2 overexpression predicts worse immunotherapy efficacy.Conclusion Our findings provide novel insights into the role of SKP2 in regulating the tumor immune microenvironment,suggesting targeting SKP2 as a promising strategy to enhance immunotherapy efficacy in pan-cancer settings.展开更多
基金supported by the National Natural Science Foundation of China(81470434,81503074,and81670265)the Science and Technology Project of Hunan Province,China(2015RS4040)+1 种基金the Administration of Traditional Chinese Medicine of Hunan Province,China(201578)the Health and Family-planning Commission of Hunan Province,China(B2015-48)
文摘Recently,Richter et al.[1]revealed the potential functions of the interaction between the serine/threonine kinase Tank-binding kinase 1（TBK1）and the autophagy receptor optineurin（OPTN）.The TBK1-OPTN axis targets damaged mitochondria for degradation via PINK1/parkin-mediated mitophagy[2,3].Indeed,TBK1 can phosphorylate OPTN at Ser177,Ser473,or Ser513 to enhance the binding capacity of OPTN with poly-ubiquitin（poly-UB）chains.Conversely,
基金supported by the National Natural Science Foundation of China (81503074)
文摘Recently, Khayachi et al.;showed that fragile X mental retardation protein （FMRP） is an active substrate of the small ubiquitin-like modifier （SUMO） pathway in neurons.FMRP SUMOylation is induced by the activation of metabotropic glutamate receptors （mGlu5Rs）. FMRP
基金supported by grants from National Key Basic Research and Development Program (Grant No.2010CB912801)National Natural Science Foundation of China (Grant No. 31071157 and 31271404)
文摘Bacterial small RNAs （sRNAs） are an emerging class of regulatory RNAs of about 40-500 nucleotides in length and, by binding to their target mRNAs or proteins, get involved in many biological processes such as sensing environmental changes and regulating gene expres- sion. Thus, identification of bacterial sRNAs and their targets has become an important part of sRNA biology. Current strategies for discovery of sRNAs and their targets usually involve bioinformatics prediction followed by experimental validation, emphasizing a key role for bioinformatics prediction. Here, therefore, we provided an overview on prediction methods, focusing on the merits and limita- tions of each class of models. Finally, we will present our thinking on developing related bioinformafics models in future.
基金supported by grants from the National Natural Science Foundation of China(No.81970431)the Hunan Provincial Natural Science Foundation of China(No.2023JJ50136)
文摘To the Editor:Pathological cardiac hypertrophy is commonly stimulated by stress or induced by cardiovascular diseases,such as hypertension and myocardial infarction.A sustained pathological hypertrophic response can lead to declines in diastolic and systolic functions and eventually develop heart failure.Angiotensin II(Ang II)can mediate cardiac hypertrophy through the angiotensin II type 1 receptor(AT1R).^([1])
基金supported by grants from the National Natural Science Foundation of China(81770794 and 314010010)the Special Grants from the Guangzhou Pearl River Young Talents of Science and Technology(201610010079,China)the Fundamental Research Funds for the Central Universities(21617457,China)
文摘Interleukin-27(IL-27),a heterodimeric cytokine,plays a protective role in diabetes.Ghrelin,a gastric hormone,provides a hunger signal to the central nervous system to stimulate food intake.The relationship between IL-27 and ghrelin is still unexplored.Here we investigated that signal transducer and activator of transcription 3(STAT3)—mechanistic target of rapamycin(mTOR)signaling mediates the suppression of ghrelin induced by IL-27.Co-localization of interleukin 27 receptor subunit alpha(WSX-1)and ghrelin was observed in mouse and human gastric mucosa.Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57 BL/6 J mice and high-fat diet-induced-obese mice.IL-27 inhibited the production of ghrelin in mHypoE-N42 cells.Inhibition of mTOR activity induced by mTOR siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells.Stat 3 siRNA also abolished the inhibitory effect of IL-27 on ghrelin.IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells.In conclusion,IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.
基金supported by grants provided by National Natural Science Foundation of China(grant Nos.82103223 and 82303165)Peking University People’s Hospital Scientific Research Development Funds(grant No.RDX2022-01)+2 种基金Peking University Clinical Scientist Training Program(grant No.BMU2023PYJH015)Beijing Physician Scientist Training Project(BJPSTP-2024-10)National Institutes of Health(grant No.R01CA255643).
文摘Background S-Phase kinase associated protein 2(SKP2)is a key regulator of the cell cycle and proliferation linked to cancer development.Our recent study has revealed that knocking out Skp2 in a mouse model significantly activates anti-tumor immunity.Although several studies have examined SKP2 in relation to the tumor immune microenvironment using public datasets,a comprehensive pan-cancer evaluation that integrates multi-omics layers and in vivo validation has remained limited.Methods In this study,we integrated multi-omics data from diverse public datasets to comprehensively analyze SKP2 expression characteristics and its relationship to tumor immunity across pan-cancer.A multiplex immunofluorescence assay was performed on tumors from Skp2 knockout and Skp2-intact mouse models for validation.Results Our findings indicate that SKP2 is overexpressed in various cancer types,leading to poor prognosis.Single-cell transcriptomic analyses further revealed that SKP2 is predominantly expressed in malignant and immune cells.Notably,a multiplex immunofluorescence assay on tumors from Skp2 knockout and Skp2-intact mouse models and pan-cancer data unveiled a correlation between SKP2 and the“immune-cold”microenvironment,which,possibly linked to the weakened antigen presentation,reduced secretion of chemokines in SKP2-overexpressing cancers.Additionally,we observed that SKP2 overexpression predicts worse immunotherapy efficacy.Conclusion Our findings provide novel insights into the role of SKP2 in regulating the tumor immune microenvironment,suggesting targeting SKP2 as a promising strategy to enhance immunotherapy efficacy in pan-cancer settings.
