Objective: To investigate the effect of SLC6A8 on the proliferation of liver cancer cells by regulating mitophagy through BNIP3L. Methods: The expression of the SLC6A8 gene in liver cancer tissues was analyzed using t...Objective: To investigate the effect of SLC6A8 on the proliferation of liver cancer cells by regulating mitophagy through BNIP3L. Methods: The expression of the SLC6A8 gene in liver cancer tissues was analyzed using the TCGA database, and its correlation with BNIP3L expression was assessed. RT-PCR and Western blot techniques were employed to detect the expression of SLC6A8 and BNIP3L in human liver cancer Huh-7 and Hep3B cells. Immunofluorescence labeling and CCK-8 assay were used to observe mitochondrial autophagy and cell proliferation rate in SLC6A8-overexpressing Huh-7 and Hep3B cells. Evaluate the proliferation rate of SLC6A8-overexpressing Huh-7 and Hep3B cells after silencing BNIP3L using the CCK-8 detection method. Results: SLC6A8 was significantly overexpressed in liver cancer tissues and positively correlated with BNIP3L expression. Overexpression of SLC6A8 significantly promoted mitochondrial autophagy and proliferation of Huh-7 and Hep3B cells. Additionally, SLC6A8 overexpression significantly enhanced the expression of BNIP3L mRNA and protein. Upon BNIP3L silencing, the proliferative effect of SLC6A8 overexpression on liver cancer cells was reversed. Conclusion: High expression of SLC6A8 in liver cancer tissues is positively correlated with BNIP3L, and overexpression of SLC6A8 promotes mitochondrial autophagy and liver cancer cell proliferation. Silencing BNIP3L can reverses the effect of overexpression of SLC6A8 on liver cancer cell proliferation. This provides new targets and strategies for the treatment of liver cancer.展开更多
Acute myeloid leukemia(AML)is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming.Here,we applied spatial metabolomics to achieve high-throughput,in situ identification of m...Acute myeloid leukemia(AML)is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming.Here,we applied spatial metabolomics to achieve high-throughput,in situ identification of metabolites within the liver metastases of AML mice.Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics.This study showed a downregulation in arginine's contribution to polyamine biosynthesis and urea cycle,coupled with an upregulation of the creatine metabolism.The upregulation of creatine synthetases Gatm and Gamt,as well as the creatine transporter Slc6a8,resulted in a marked accumulation of creatine within tumor foci.This process further enhances oxidative phosphorylation and glycolysis of leukemia cells,thereby boosting ATP production to foster proliferation and infiltration.Importantly,we discovered that inhibiting Slc6a8 can counter these detrimental effects,offering a new strategy for treating AML by targeting metabolic pathways.展开更多
基金Research Fund for Young and Middle-aged Teachers'Basic Research Ability Promotion Project of Guangxi Universities in 2021(No.2021KY0539)。
文摘Objective: To investigate the effect of SLC6A8 on the proliferation of liver cancer cells by regulating mitophagy through BNIP3L. Methods: The expression of the SLC6A8 gene in liver cancer tissues was analyzed using the TCGA database, and its correlation with BNIP3L expression was assessed. RT-PCR and Western blot techniques were employed to detect the expression of SLC6A8 and BNIP3L in human liver cancer Huh-7 and Hep3B cells. Immunofluorescence labeling and CCK-8 assay were used to observe mitochondrial autophagy and cell proliferation rate in SLC6A8-overexpressing Huh-7 and Hep3B cells. Evaluate the proliferation rate of SLC6A8-overexpressing Huh-7 and Hep3B cells after silencing BNIP3L using the CCK-8 detection method. Results: SLC6A8 was significantly overexpressed in liver cancer tissues and positively correlated with BNIP3L expression. Overexpression of SLC6A8 significantly promoted mitochondrial autophagy and proliferation of Huh-7 and Hep3B cells. Additionally, SLC6A8 overexpression significantly enhanced the expression of BNIP3L mRNA and protein. Upon BNIP3L silencing, the proliferative effect of SLC6A8 overexpression on liver cancer cells was reversed. Conclusion: High expression of SLC6A8 in liver cancer tissues is positively correlated with BNIP3L, and overexpression of SLC6A8 promotes mitochondrial autophagy and liver cancer cell proliferation. Silencing BNIP3L can reverses the effect of overexpression of SLC6A8 on liver cancer cell proliferation. This provides new targets and strategies for the treatment of liver cancer.
基金supported by the National Natural Science Foundation of China(No.81770124)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(RC20210190,China)。
文摘Acute myeloid leukemia(AML)is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming.Here,we applied spatial metabolomics to achieve high-throughput,in situ identification of metabolites within the liver metastases of AML mice.Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics.This study showed a downregulation in arginine's contribution to polyamine biosynthesis and urea cycle,coupled with an upregulation of the creatine metabolism.The upregulation of creatine synthetases Gatm and Gamt,as well as the creatine transporter Slc6a8,resulted in a marked accumulation of creatine within tumor foci.This process further enhances oxidative phosphorylation and glycolysis of leukemia cells,thereby boosting ATP production to foster proliferation and infiltration.Importantly,we discovered that inhibiting Slc6a8 can counter these detrimental effects,offering a new strategy for treating AML by targeting metabolic pathways.
