Aim:Hepatocellular carcinoma(HCC)remains a major challenge due to poor prognosis.This study investigates 3-methylcytidine(m^(3)C)RNA methylation regulators to elucidate their roles in HCC and to develop a prognostic s...Aim:Hepatocellular carcinoma(HCC)remains a major challenge due to poor prognosis.This study investigates 3-methylcytidine(m^(3)C)RNA methylation regulators to elucidate their roles in HCC and to develop a prognostic scoring system for clinical application.Methods:We integrated data from 486 HCC patients[The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)datasets]and 16 pairs of clinical tissue samples.The expression,mutation profiles,and prognostic significance of 6 m^(3)C regulators were analyzed.Functional assays,including cell proliferation and migration,were performed,alongside immune infiltration analysis using single-sample gene set enrichment analysis(ssGSEA).Finally,an m^(3)C scoring system was constructed to evaluate prognostic potential.Results:Most m^(3)C regulators(except METTL8)were upregulated in HCC tissues.Knockdown of METTL2,METTL6,ALKBH1,or ALKBH3,as well as overexpression of METTL8,inhibited HCC cell proliferation and migration.Two distinct m^(3)C modification modes were identified,each associated with unique clinical features.The m^(3)C score was positively correlated with longer overall survival in high-score patients and was associated with tumor mutation burden(TMB)and expression of PD-1 and CTLA4,suggesting its potential to predict immunotherapy response.Conclusion:This study highlights the genetic variation and prognostic relevance of m^(3)C methylation regulators in HCC and introduces a novel scoring system for prognosis prediction,providing a potential tool to guide HCC treatment strategies.展开更多
Background and Aims:Acetaminophen(APAP)-induced liver injury(AILI)has an increasing incidence worldwide.However,the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently...Background and Aims:Acetaminophen(APAP)-induced liver injury(AILI)has an increasing incidence worldwide.However,the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently available.The study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in vivo.Methods:We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4(BTF3L4)was the only outlier transcription factor overexpressed in the AILI model in mice.BTF3L4 overexpression increased the degree of liver injury in the AILI model.Results:BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial function.Increased BTF3L4 expression increases the degree of apoptosis,reactive oxygen species generation,and oxidative stress,which induces cell death and liver injury.The damage of mitochondrial function by BTF3L4 triggers a cascade of events,including reactive oxygen species accumulation and oxidative stress.According to the available AILI data,BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of AILI.Conclusions:Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.展开更多
基金This research was funded by the National Natural Science Foundation of China(No.82372693).
文摘Aim:Hepatocellular carcinoma(HCC)remains a major challenge due to poor prognosis.This study investigates 3-methylcytidine(m^(3)C)RNA methylation regulators to elucidate their roles in HCC and to develop a prognostic scoring system for clinical application.Methods:We integrated data from 486 HCC patients[The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)datasets]and 16 pairs of clinical tissue samples.The expression,mutation profiles,and prognostic significance of 6 m^(3)C regulators were analyzed.Functional assays,including cell proliferation and migration,were performed,alongside immune infiltration analysis using single-sample gene set enrichment analysis(ssGSEA).Finally,an m^(3)C scoring system was constructed to evaluate prognostic potential.Results:Most m^(3)C regulators(except METTL8)were upregulated in HCC tissues.Knockdown of METTL2,METTL6,ALKBH1,or ALKBH3,as well as overexpression of METTL8,inhibited HCC cell proliferation and migration.Two distinct m^(3)C modification modes were identified,each associated with unique clinical features.The m^(3)C score was positively correlated with longer overall survival in high-score patients and was associated with tumor mutation burden(TMB)and expression of PD-1 and CTLA4,suggesting its potential to predict immunotherapy response.Conclusion:This study highlights the genetic variation and prognostic relevance of m^(3)C methylation regulators in HCC and introduces a novel scoring system for prognosis prediction,providing a potential tool to guide HCC treatment strategies.
基金funded by Independent Funds of the Key Laboratory(CBSKL2022ZZ34)Xijing Hospital Booster Program(XJZT21CM04).
文摘Background and Aims:Acetaminophen(APAP)-induced liver injury(AILI)has an increasing incidence worldwide.However,the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently available.The study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in vivo.Methods:We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4(BTF3L4)was the only outlier transcription factor overexpressed in the AILI model in mice.BTF3L4 overexpression increased the degree of liver injury in the AILI model.Results:BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial function.Increased BTF3L4 expression increases the degree of apoptosis,reactive oxygen species generation,and oxidative stress,which induces cell death and liver injury.The damage of mitochondrial function by BTF3L4 triggers a cascade of events,including reactive oxygen species accumulation and oxidative stress.According to the available AILI data,BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of AILI.Conclusions:Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.
