Background and Aims:Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma(HCC)patients while the underlying mechanism of metastasis remains elusive.In our study,procoll...Background and Aims:Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma(HCC)patients while the underlying mechanism of metastasis remains elusive.In our study,procollagen-lysine,2-oxoglutarate 5-dioxygenase 2(PLOD2)was shown to be involved in the process of metastasis in HCC.Methods:The Cancer Genome Atlas(TCGA)database and HCC tissue microarrays were used to evaluate the expression of genes.In vitro migration,invasion,in vivo subcutaneous tumor model and in vivo lung metastasis assays were used to determine the role of PLOD2 in tumor growth and metastasis in HCC.RNA sequencing and gene set enrichment analysis were performed to uncover the downstream factor of PLOD2 in HCC cells.A luciferase reporter assay was performed to evaluate the interaction between PLOD2 and interferon regulatory factor 5(IRF5).Results:The expression of PLOD2 in HCC tissues was higher than that in adjacent tissues,and increased PLOD2 expression was often found in advanced tumors and was correlated with poor prognosis in HCC patients.In vitro experiments,knockdown of PLOD2 reduced the migration and invasion of human HCC cells.Loss of PLOD2 suppressed human HCC growth and metastasis in a subcutaneous tumor model and a lung metastasis model.Baculoviral IAP repeat containing 3(BIRC3)was proven to be the downstream factor of PLOD2 in human HCC cells.In addition,PLOD2 was transcriptionally regulated by IRF5 in HCC cells.Conclusions:High expression of PLOD2 was regulated by IRF5,which was correlated with the poor survival of HCC patients.PLOD2 enhanced HCC metastasis via BIRC3,suggesting that PLOD2 might be a valuable prognostic biomarker for HCC treatment.展开更多
Introduction:Pathogenic variants inPLOD3,encoding lysyl hydroxylase-3(LH3),can cause a hereditary connective tissue disorder that has rarely been reported.It is a multi-system disease,presenting with craniofacial dysm...Introduction:Pathogenic variants inPLOD3,encoding lysyl hydroxylase-3(LH3),can cause a hereditary connective tissue disorder that has rarely been reported.It is a multi-system disease,presenting with craniofacial dysmorphisms,skeletal and eye manifestations,sensorineural hearing loss,and variable skin manifestations.Severe central nervous system involvement has not been reported.Case presentation:A 10-month-old girl was admitted with development delay and clustered epileptic spasms.Hypertelorism,an upturned nose,and low-set ears were noted in physical examination.Cerebral magnetic resonance imaging showed multiple intracranial malacias and bleeding foci,extensive abnormal signals in the white matter,and obvious brain atrophy,which was consistent with cerebral small vessel disease(SVD).Electroencephalography suggested hypsarrhythmia.The vertebrae were flattened.The distal end of the metacarpal bone in the left hand was irregular.She was diagnosed with West syndrome.Whole-exome sequencing revealed a novel homozygous variant of c.12161218delCTC(p.L406del)inPLOD3,which was found to be inherited from her heterozygous parents.Conclusion:We report a patient with pathogenicPLOD3 mutation who presented with cerebral SVD.This report expands the phenotypic spectrum of LH3 deficiency.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81902473,82172815,and 82103601).
文摘Background and Aims:Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma(HCC)patients while the underlying mechanism of metastasis remains elusive.In our study,procollagen-lysine,2-oxoglutarate 5-dioxygenase 2(PLOD2)was shown to be involved in the process of metastasis in HCC.Methods:The Cancer Genome Atlas(TCGA)database and HCC tissue microarrays were used to evaluate the expression of genes.In vitro migration,invasion,in vivo subcutaneous tumor model and in vivo lung metastasis assays were used to determine the role of PLOD2 in tumor growth and metastasis in HCC.RNA sequencing and gene set enrichment analysis were performed to uncover the downstream factor of PLOD2 in HCC cells.A luciferase reporter assay was performed to evaluate the interaction between PLOD2 and interferon regulatory factor 5(IRF5).Results:The expression of PLOD2 in HCC tissues was higher than that in adjacent tissues,and increased PLOD2 expression was often found in advanced tumors and was correlated with poor prognosis in HCC patients.In vitro experiments,knockdown of PLOD2 reduced the migration and invasion of human HCC cells.Loss of PLOD2 suppressed human HCC growth and metastasis in a subcutaneous tumor model and a lung metastasis model.Baculoviral IAP repeat containing 3(BIRC3)was proven to be the downstream factor of PLOD2 in human HCC cells.In addition,PLOD2 was transcriptionally regulated by IRF5 in HCC cells.Conclusions:High expression of PLOD2 was regulated by IRF5,which was correlated with the poor survival of HCC patients.PLOD2 enhanced HCC metastasis via BIRC3,suggesting that PLOD2 might be a valuable prognostic biomarker for HCC treatment.
文摘Introduction:Pathogenic variants inPLOD3,encoding lysyl hydroxylase-3(LH3),can cause a hereditary connective tissue disorder that has rarely been reported.It is a multi-system disease,presenting with craniofacial dysmorphisms,skeletal and eye manifestations,sensorineural hearing loss,and variable skin manifestations.Severe central nervous system involvement has not been reported.Case presentation:A 10-month-old girl was admitted with development delay and clustered epileptic spasms.Hypertelorism,an upturned nose,and low-set ears were noted in physical examination.Cerebral magnetic resonance imaging showed multiple intracranial malacias and bleeding foci,extensive abnormal signals in the white matter,and obvious brain atrophy,which was consistent with cerebral small vessel disease(SVD).Electroencephalography suggested hypsarrhythmia.The vertebrae were flattened.The distal end of the metacarpal bone in the left hand was irregular.She was diagnosed with West syndrome.Whole-exome sequencing revealed a novel homozygous variant of c.12161218delCTC(p.L406del)inPLOD3,which was found to be inherited from her heterozygous parents.Conclusion:We report a patient with pathogenicPLOD3 mutation who presented with cerebral SVD.This report expands the phenotypic spectrum of LH3 deficiency.
