Loss of COP1 expression determines poor prognosisin patients with gastric cancer.
Previous studies have suggested conflicting roles for the E3 ubiquitin ligase COP1 in tumorigenesis, providing evidence that both the oncoprotein c-Jun and the tumor suppressor p53 may be COP1 targets. In the present study, we focused on the clinical significance of COP1 expression in gastric cancer cases and analyzed the malignant behavior of COP1‑knockdown gastric cancer cells in vitro. We analyzed COP1 expression in cancer lesions and the corresponding normal mucosa to demonstrate the clinical significance of COP1 expression in 133 cases of gastric cancer. We also investigated the relationship between COP1 expression and cell proliferation and the association of COP1 with c‑Jun transcriptional target genes, such as MMP1, MMP7 and MMP10. The expression of COP1 mRNA was significantly lower in gastric cancer tissues compared to the corresponding normal mucosa (P=0.049). In multivariate analysis for overall survival, we found that COP1 expression was an independent prognostic factor in gastric cancer. Knockdown of COP1 expression in the gastric cancer cell lines MKN‑45 and NUGC4 promoted proliferation, and significant associations between COP1 expression and MMP1, MMP7 and MMP10 were also observed in knockdown assays. In conclusion, the present study suggests that loss of COP1 expression may be a novel indicator for the biological aggressiveness in gastric cancer.
Department of Surgery, Beppu Hospital, Kyushu University, Beppu, Oita 874-0838, Japan.
Genta
G
Sawada
Hiroki
H
Ueo
Tae
T
Matsumura
Ryutaro
R
Uchi
Masahisa
M
Ishibashi
Kosuke
K
Mima
Junji
J
Kurashige
Yusuke
Y
Takahashi
Sayuri
S
Akiyoshi
Tomoya
T
Sudo
Keishi
K
Sugimachi
Yuichiro
Y
Doki
Masaki
M
Mori
Koshi
K
Mimori
D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases; D053506:Matrix Metalloproteinase 10; D020783:Matrix Metalloproteinase 7; D020781:Matrix Metalloproteinase 1