human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: UNLABELLED Hepatocellular carcinoma ( HCC ) is a major liver malignancy . We previously demonstrated that deregulation of epigenetic regulators is a common event in human HCC . Suppressor of variegation 3-9 homolog 1 ( SUV39H1 ) , the prototype of histone methyltransferase , is the major enzyme responsible for histone H3 lysine 9 trimethylation , which , essentially , is involved in heterochromatin formation , chromosome segregation , and mitotic progression . However , the implication of SUV39H1 in hepatocarcinogenesis remains elusive . In this study , we found that SUV39H1 was frequently up-regulated in human HCCs and was significantly associated with increased Ki67 expression ( P &lt ; 0.001 ) and the presence of venous invasion ( P = 0.017 ) . To investigate the role of SUV39H1 in HCC development , both gain- and loss-of-function models were established . SUV39H1 overexpression remarkably enhanced HCC cell clonogenicity , whereas knockdown of SUV39H1 substantially suppressed HCC cell proliferation and induced cell senescence . In addition , ectopic expression of SUV39H1 increased the migratory ability of HCC cells , whereas a reduced migration rate was observed in SUV39H1 knockdown cells . The significance of SUV39H1 in HCC was further demonstrated in a nude mice model ; SUV39H1 knockdown drastically inhibited in vivo tumorigenicity and abolished pulmonary metastasis of HCC cells . We also identified microRNA-125b ( miR-125b ) as a post-transcriptional regulator of SUV39H1 . Ectopic expression of miR-125b inhibited SUV39H1 3'-untranslated-region-coupled luciferase activity and suppressed endogenous SUV39H1 expression at both messenger RNA and protein levels . We have previously reported frequent down-regulation of miR-125b in HCC . Interestingly , miR-125b level was found to be inversely correlated with SUV39H1 expression ( P = 0.001 ) in clinical specimens . Our observations suggested that miR-125b down-regulation may account for the aberrant SUV39H1 level in HCC . CONCLUSION Our study demonstrated that SUV39H1 up-regulation contributed to HCC development and metastasis . The tumor-suppressive miR-125b served as a negative regulator of SUV39H1 .
    OUTPUT:

agent
enabling replicative immortality;activating invasion and metastasis
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: UNLABELLED Hepatocellular carcinoma ( HCC ) is a major liver malignancy . We previously demonstrated that deregulation of epigenetic regulators is a common event in human HCC . Suppressor of variegation 3-9 homolog 1 ( SUV39H1 ) , the prototype of histone methyltransferase , is the major enzyme responsible for histone H3 lysine 9 trimethylation , which , essentially , is involved in heterochromatin formation , chromosome segregation , and mitotic progression . However , the implication of SUV39H1 in hepatocarcinogenesis remains elusive . In this study , we found that SUV39H1 was frequently up-regulated in human HCCs and was significantly associated with increased Ki67 expression ( P &lt ; 0.001 ) and the presence of venous invasion ( P = 0.017 ) . To investigate the role of SUV39H1 in HCC development , both gain- and loss-of-function models were established . SUV39H1 overexpression remarkably enhanced HCC cell clonogenicity , whereas knockdown of SUV39H1 substantially suppressed HCC cell proliferation and induced cell senescence . In addition , ectopic expression of SUV39H1 increased the migratory ability of HCC cells , whereas a reduced migration rate was observed in SUV39H1 knockdown cells . The significance of SUV39H1 in HCC was further demonstrated in a nude mice model ; SUV39H1 knockdown drastically inhibited in vivo tumorigenicity and abolished pulmonary metastasis of HCC cells . We also identified microRNA-125b ( miR-125b ) as a post-transcriptional regulator of SUV39H1 . Ectopic expression of miR-125b inhibited SUV39H1 3'-untranslated-region-coupled luciferase activity and suppressed endogenous SUV39H1 expression at both messenger RNA and protein levels . We have previously reported frequent down-regulation of miR-125b in HCC . Interestingly , miR-125b level was found to be inversely correlated with SUV39H1 expression ( P = 0.001 ) in clinical specimens . Our observations suggested that miR-125b down-regulation may account for the aberrant SUV39H1 level in HCC . CONCLUSION Our study demonstrated that SUV39H1 up-regulation contributed to HCC development and metastasis . The tumor-suppressive miR-125b served as a negative regulator of SUV39H1 .
    OUTPUT:
