TY - JOUR
T1 - Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers
AU - Takahashi, Y.
AU - Sawada, G.
AU - Kurashige, J.
AU - Uchi, R.
AU - Matsumura, T.
AU - Ueo, H.
AU - Takano, Y.
AU - Eguchi, H.
AU - Sudo, T.
AU - Sugimachi, K.
AU - Yamamoto, H.
AU - Doki, Y.
AU - Mori, M.
AU - Mimori, K.
N1 - Funding Information:
The present study was supported in part by the following grants and foundation; CREST, Japan Science and Technology Agency (JST), the Funding Program for Next Generation World-Leading Researchers (LS094), and Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant number 25861199. We thank T Shimooka, K Oda, M Kasagi, S Kono, T Kawano and M Aoyagi for their technical assistance.
PY - 2014
Y1 - 2014
N2 - Background:We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.Methods:We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR.Results:CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-β signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients.Conclusion:PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.
AB - Background:We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.Methods:We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR.Results:CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-β signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients.Conclusion:PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.
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U2 - 10.1038/bjc.2013.698
DO - 10.1038/bjc.2013.698
M3 - Article
C2 - 24196785
AN - SCOPUS:84891883037
VL - 110
SP - 164
EP - 171
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 1
ER -