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CSIG promotes hepatocellular carcinoma proliferation by activating c-MYC expression.
- Source :
-
Oncotarget [Oncotarget] 2015 Mar 10; Vol. 6 (7), pp. 4733-44. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Adult
Aged
Animals
Apoptosis
Blotting, Western
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Case-Control Studies
Cellular Senescence
Female
Follow-Up Studies
Humans
Immunoenzyme Techniques
Immunoprecipitation
Liver Neoplasms genetics
Liver Neoplasms metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasm Staging
Pregnancy Proteins antagonists & inhibitors
Pregnancy Proteins genetics
Prognosis
Proto-Oncogene Proteins c-myc genetics
RNA, Messenger genetics
RNA, Small Interfering genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Proteins antagonists & inhibitors
Ribosomal Proteins genetics
Tumor Cells, Cultured
Ubiquitination
Xenograft Model Antitumor Assays
Carcinoma, Hepatocellular pathology
Cell Proliferation
Liver metabolism
Liver Neoplasms pathology
Pregnancy Proteins metabolism
Proto-Oncogene Proteins c-myc metabolism
Ribosomal Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25749381
- Full Text :
- https://doi.org/10.18632/oncotarget.2900