title: Facilitation of liver cancer SMCC7721 cell aging by sirtuin 4 via inhibiting JAK2/STAT3 signal pathway.
abstract: Liver cancer severely threatens public health. Molecular targeted treatment is the further of cancer treatment. The functional role of Sir-related enzymes 4 (sirtuin 4) in treating liver cancer still requires further investigation. This study aimed to elucidate the effect of sirtuin 4 on aging of SMCC7721 liver cancer cell line, to underlying molecular mechanism and potential application in clinics.
  
  
  
  Adriamycin-induced aging model was established on SMCC7721 liver cancer cell line. Sirtuin 4 over-expression or siRNA plasmid was transfected. Cell aging was measured by β-galactosidase approach. Aging-related proteins P53 and P16 were quantified in Western blot, which also examined activation of Janus kinase 2 (JAK2) signal pathway. CP-690550 was used to suppress JAK2 signal pathway for measuring aging status of SMCC7721 cells.
  
  
  
  In aged SMCC7721 cells, sirtuin 4 was up-regulated, whilst P53 and P16 protein levels were elevated, in accompanied with JAK2/STAT3 signal pathway. Transfection of sirtuin 4 over-expression plasmid or siRNA increased or decreased sirtuin 4 expression. Adriamycin-induced aging was enhanced or suppressed, accompanied with inhibited or potentiated JAK2 signal pathway in sirtuin 4 up-regulation or down-regulation cells, respectively. The usage of JAK2 signal inhibitor, CP-690550, enhanced Adriamycin-induced cell aging.
  
  
  
  Sirtuin 4 facilitates Adriamycin-induced aging of SMCC7721 liver cancer cells via inhibiting JAK2/STAT3 signal pathway, thus providing one novel anti-cancer strategy.
authors.affiliation: Interventional Radiology Institute, Sun Yat-sen University, Guangzhou, Guangdong, China. hongshanmk@163.com.
authors.forename: X-H
authors.initials: XH
authors.lastname: Xia
authors.forename: C-J
authors.initials: CJ
authors.lastname: Xiao
authors.forename: H
authors.initials: H
authors.lastname: Shan
mesh_terms: D045744:Cell Line, Tumor; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004317:Doxorubicin; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D037761:Sirtuins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D024101:Mitochondrial Proteins; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C479163:tofacitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C525357:SIRT4 protein, human; D037761:Sirtuins