Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers

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 amplif...

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Veröffentlicht in:British journal of cancer 2014-01, Vol.110 (1), p.164-171
Hauptverfasser: Takahashi, Y, Sawada, G, Kurashige, J, Uchi, R, Matsumura, T, Ueo, H, Takano, Y, Eguchi, H, Sudo, T, Sugimachi, K, Yamamoto, H, Doki, Y, Mori, M, Mimori, K
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Sprache:eng
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Zusammenfassung: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-1 siRNA 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2013.698