CSIG promotes hepatocellular carcinoma proliferation by activating c-MYC expression.
Cellular senescence-inhibited gene (CSIG) protein significantly prolongs the progression of replicative senescence, but its role in tumorigenesis is unclear. To reveal the role of CSIG in HCC, we determined its expression in HCC tissues and surrounding tissues and its functions in tumor cell proliferation in vitro and in vivo. CSIG protein was overexpressed in 86.4% of the human HCC cancerous tissues as compared with matched surrounding tissues, and its protein expression was greater in HCC cells than the non-transformed hepatic cell line L02. Furthermore, upregulation of CSIG significantly increased the colony formation of SMMC7721 and HepG2 cells, and silencing CSIG could induce cell cycle arrest and cell apoptosis. The tumorigenic ability of CSIG was confirmed in vivo in a mouse xenograft model. Our results showed that CSIG promoted the proliferation of HepG2 and SMMC7721 cells in vivo. Finally, CSIG protein directly interacted with c-MYC protein and increased c-MYC protein levels; the ubiquitination and degradation of c-MYC protein was increased with knockdown of CSIG. CSIG could also increase the expression of c-MYC protein in SMMC7721 cells in vivo, and it was noted that the level of c-MYC protein was also elevated in most human cancerous tissues with high level of CSIG.
The Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
Qian
Q
Cheng
The Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
Fuwen
F
Yuan
Department of Microbiology, Peking University Health Science Center, Beijing, China.
Fengmin
F
Lu
Department of Pathology, Peking University Health Science Center, Beijing, China.
Bo
B
Zhang
The Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
Tianda
T
Chen
Department of Microbiology, Peking University Health Science Center, Beijing, China.
Xiangmei
X
Chen
Department of Histology and Embryology, Peking University Health Science Center, Beijing, China.
Yuan
Y
Cheng
The Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
Na
N
Li
The Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
Liwei
L
Ma
The Peking University Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
Tanjun
T
Tong
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D016922:Cellular Senescence; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D054875:Ubiquitination; D023041:Xenograft Model Antitumor Assays
D011257:Pregnancy Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C117409:RSL1D1 protein, human; D012269:Ribosomal Proteins
CSIG; HCC; MYC; proliferation; protein degradation