Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-associated death.Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis,metastasis,and prognosis.Choline is ...Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-associated death.Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis,metastasis,and prognosis.Choline is an essential nutrient related to prolonged survival and reduced risk of HCC.However,it remains unclear whether this phenomenon is mediated by autophagy.Methods:Two HCC cell lines(HUH-7 and Hep3B)were used in the present study.Cell growth was evaluated by cell counting kit 8(CCK-8),colony formation,and in vivo mouse xenografts assays.Cell motility was calculated by wound healing and transwell assays.Autophagosomes were measured by transmission electron microscope(TEM),and autophagy flux was detected by mRFP-GFP-labeled LC3 protein.The mRNA level of genes was measured by quantitative real-time polymerase chain reaction(qRT-PCR).The protein levels were detected by Western blotting(WB).Results:We found that choline inhibited the proliferation,migration,and invasion of HCC cells by downregulating autophagy in vitro and in vivo.Upregulated expression of the solute carrier family 5 member 7(SLC5A7),a specific choline transporter,correlated with better HCC prognosis.We further discovered that choline could promote SLC5A7 expression,upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway,and attenuate autophagy.Finally,we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo.Conclusions:Our findings provide novel insights into choline-mediated autophagy in HCC,providing the foothold for its future application in HCC treatment.展开更多
Accumulating studies have demonstrated that hyperbaric oxygen(HBO)treatment alleviates spinal cord injury(SCI).However,the underlying mechanism by which HBO alleviates SCI remains to be elucidated.In this study,we per...Accumulating studies have demonstrated that hyperbaric oxygen(HBO)treatment alleviates spinal cord injury(SCI).However,the underlying mechanism by which HBO alleviates SCI remains to be elucidated.In this study,we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI.We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice.We found 76 differentially co-expressed genes in sham-operated mice,SCI mice,and HBO-treated SCI mice.Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis,we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component,biological process,and molecular function.We also found enriched functional pathways including ferroptosis,calcium signaling pathway,serotonergic synapse,hypoxia-inducible factor-1 signaling pathway,cholinergic synapse,and neuroactive ligand-receptor interaction.We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1(heat shock protein beta 1),Hmox1(heme oxygenase 1),Ftl1(ferritin light polypeptide 1),Tnc(tenascin C)and Igfbp3(insulin-like growth factor binding protein 3)and increased the expression of Slc5a7(solute carrier family 5 choline transporter member 7)after SCI.These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment.Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.展开更多
基金Basic and Applied Basic Research Foundation of Guangdong Province,China(grant No.2020A1515110682)Guangdong Provincial Science and Technology Project(grant No.2017A040406008)+1 种基金National Natural Science Foundation of China(grant Nos.81973016,82103825)Postdoctoral Science Foundation of China(grant No.2020M683135).
文摘Background:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-associated death.Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis,metastasis,and prognosis.Choline is an essential nutrient related to prolonged survival and reduced risk of HCC.However,it remains unclear whether this phenomenon is mediated by autophagy.Methods:Two HCC cell lines(HUH-7 and Hep3B)were used in the present study.Cell growth was evaluated by cell counting kit 8(CCK-8),colony formation,and in vivo mouse xenografts assays.Cell motility was calculated by wound healing and transwell assays.Autophagosomes were measured by transmission electron microscope(TEM),and autophagy flux was detected by mRFP-GFP-labeled LC3 protein.The mRNA level of genes was measured by quantitative real-time polymerase chain reaction(qRT-PCR).The protein levels were detected by Western blotting(WB).Results:We found that choline inhibited the proliferation,migration,and invasion of HCC cells by downregulating autophagy in vitro and in vivo.Upregulated expression of the solute carrier family 5 member 7(SLC5A7),a specific choline transporter,correlated with better HCC prognosis.We further discovered that choline could promote SLC5A7 expression,upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway,and attenuate autophagy.Finally,we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo.Conclusions:Our findings provide novel insights into choline-mediated autophagy in HCC,providing the foothold for its future application in HCC treatment.
基金supported by the Natural Science Foundation of Beijing, No.7202055(to XHL)
文摘Accumulating studies have demonstrated that hyperbaric oxygen(HBO)treatment alleviates spinal cord injury(SCI).However,the underlying mechanism by which HBO alleviates SCI remains to be elucidated.In this study,we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI.We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice.We found 76 differentially co-expressed genes in sham-operated mice,SCI mice,and HBO-treated SCI mice.Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis,we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component,biological process,and molecular function.We also found enriched functional pathways including ferroptosis,calcium signaling pathway,serotonergic synapse,hypoxia-inducible factor-1 signaling pathway,cholinergic synapse,and neuroactive ligand-receptor interaction.We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1(heat shock protein beta 1),Hmox1(heme oxygenase 1),Ftl1(ferritin light polypeptide 1),Tnc(tenascin C)and Igfbp3(insulin-like growth factor binding protein 3)and increased the expression of Slc5a7(solute carrier family 5 choline transporter member 7)after SCI.These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment.Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.
