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
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.
