Overexpression of BIRC6 Is a Predictor of Prognosis for Colorectal Cancer.
OBJECTIVE
Inhibitors of apoptosis proteins (IAPs) have been well investigated in human cancers, where they are frequently overexpressed and associated with poor prognosis. Here we explored the role of baculoviral IAP repeat containing 6 (BIRC6), a member of IAPs, in human colorectal cancer (CRC).


METHODS
We used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method.


RESULTS
We reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS) (P = 0.001) and shorter disease-free survival (DFS) (P = 0.010). BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo.


CONCLUSIONS
Taken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy.
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Tingting
T
Hu
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
Shuqiang
S
Weng
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
Wenqing
W
Tang
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
Ruyi
R
Xue
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
She
S
Chen
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Guoxiang
G
Cai
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
Yu
Y
Cai
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
Xizhong
X
Shen
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Si
S
Zhang
Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
Ling
L
Dong
D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction; D016019:Survival Analysis; D047368:Tumor Burden
D000970:Antineoplastic Agents; C401541:BIRC6 protein, human; C503721:CCNA2 protein, human; C534699:CCNB1 protein, human; C530104:CCND1 protein, human; C475820:CCNE1 protein, human; D056751:Cyclin A2; D056744:Cyclin B1; D019927:Cyclin E; D051034:Inhibitor of Apoptosis Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D019938:Cyclin D1