Asparagine-linked glycosylation protein 1 homolog(ALG1)participates in the initial stage of protein N-glycosylation and N-glycosylation has been implicated in the process of hepatocellular carcinoma(HCC)progression.Ho...Asparagine-linked glycosylation protein 1 homolog(ALG1)participates in the initial stage of protein N-glycosylation and N-glycosylation has been implicated in the process of hepatocellular carcinoma(HCC)progression.However,whether ALG1 plays a role in human HCC remains unknown.In this study,the expression profile of ALG1 in tumorous and corresponding adjacent non-tumor tissues was analyzed.The relationship of ALG1 expression with clinical features and prognosis of HCC patients was also evaluated using immuno-histochemical method.Here we found ALG1 decreased in HCC tissues compared with adjacent normal liver tissues,which predicted an unfavorable prognosis.Combined with RNA interference,nascent proteome and glycoproteome were determined systematically in Huh7 cell line.Bioinformatics analysis indicated that the differentially expressed proteins participating in the response of ALG1 knockdown were most significantly associated with cell-cell adhesion.Functional studies confirmed that knockdown of ALG1 reduced cell adhesion capacity,and promoted cell migration.Furthermore,down-regulation of H8N2(on N-glycosite N651)and H5N4S2F1(on N-glycosite N692)from N-cadherin was identified as a feature of ALG1 knockdown.Our findings revealed that ALG1 controlled the expression of glycosylated N-cadherin and played a role in HCC migration,with implications for prognosis.展开更多
基金the financial support of the National Key Research and Development Program of China(2017YFA0505100)NSF of China(Grants 21974025 and 82121004)for this work.
文摘Asparagine-linked glycosylation protein 1 homolog(ALG1)participates in the initial stage of protein N-glycosylation and N-glycosylation has been implicated in the process of hepatocellular carcinoma(HCC)progression.However,whether ALG1 plays a role in human HCC remains unknown.In this study,the expression profile of ALG1 in tumorous and corresponding adjacent non-tumor tissues was analyzed.The relationship of ALG1 expression with clinical features and prognosis of HCC patients was also evaluated using immuno-histochemical method.Here we found ALG1 decreased in HCC tissues compared with adjacent normal liver tissues,which predicted an unfavorable prognosis.Combined with RNA interference,nascent proteome and glycoproteome were determined systematically in Huh7 cell line.Bioinformatics analysis indicated that the differentially expressed proteins participating in the response of ALG1 knockdown were most significantly associated with cell-cell adhesion.Functional studies confirmed that knockdown of ALG1 reduced cell adhesion capacity,and promoted cell migration.Furthermore,down-regulation of H8N2(on N-glycosite N651)and H5N4S2F1(on N-glycosite N692)from N-cadherin was identified as a feature of ALG1 knockdown.Our findings revealed that ALG1 controlled the expression of glycosylated N-cadherin and played a role in HCC migration,with implications for prognosis.
