Overexpression of BIRC6 Is a Predictor of Prognosis for Colorectal Cancer

Tingting Hu; Shuqiang Weng; Wenqing Tang; Ruyi Xue; She Chen; Guoxiang Cai; Yu Cai; Xizhong Shen; Si Zhang; Ling Dong

doi:10.1371/journal.pone.0125281

Overexpression of BIRC6 Is a Predictor of Prognosis for Colorectal Cancer

PLoS One. 2015 May 1;10(5):e0125281. doi: 10.1371/journal.pone.0125281. eCollection 2015.

Authors

Tingting Hu¹, Shuqiang Weng², Wenqing Tang², Ruyi Xue², She Chen³, Guoxiang Cai⁴, Yu Cai², Xizhong Shen², Si Zhang³, Ling Dong²

Affiliations

¹ 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.
² Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
³ Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract

Background and 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / diagnosis
Adenocarcinoma / drug therapy
Adenocarcinoma / genetics*
Adenocarcinoma / mortality
Antineoplastic Agents / therapeutic use
Cell Line, Tumor
Cell Proliferation / drug effects
Colorectal Neoplasms / diagnosis
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / mortality
Cyclin A2 / genetics
Cyclin A2 / metabolism
Cyclin B1 / genetics
Cyclin B1 / metabolism
Cyclin D1 / genetics
Cyclin D1 / metabolism
Cyclin E / genetics
Cyclin E / metabolism
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / genetics
Female
Gene Expression Regulation, Neoplastic*
Genetic Vectors
Humans
Inhibitor of Apoptosis Proteins / antagonists & inhibitors
Inhibitor of Apoptosis Proteins / genetics*
Inhibitor of Apoptosis Proteins / metabolism
Lentivirus / genetics
Male
Middle Aged
Neoplasm Invasiveness
Oncogene Proteins / genetics
Oncogene Proteins / metabolism
Prognosis
RNA, Small Interfering / genetics*
RNA, Small Interfering / metabolism
S Phase Cell Cycle Checkpoints / drug effects
Signal Transduction
Survival Analysis
Tumor Burden

Substances

Antineoplastic Agents
BIRC6 protein, human
CCNA2 protein, human
CCNB1 protein, human
CCND1 protein, human
CCNE1 protein, human
Cyclin A2
Cyclin B1
Cyclin E
Inhibitor of Apoptosis Proteins
Oncogene Proteins
RNA, Small Interfering
Cyclin D1

Grants and funding

This work was supported by Shanghai Science and Technology Commission (grant numbers: 10411950100 to XS, 12ZR1405300 to YC), National Natural Science Foundation of China (grant numbers: 81100344, 81173078 to SZ, 81371268 to SC, 81172273, 81272388 to LD, 81472673 to YC, 81272388, 81400628 to XS), the National Clinical Key Special Subject of China (grant number: 371 to XS), and Shanghai Pujiang Program(grant number: No.13PJD008 to GC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.