Journal
BRITISH JOURNAL OF CANCER
Volume 110, Issue 1, Pages 164-171Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.698
Keywords
colorectal cancer; PVT-1; long noncoding RNA; apoptosis; 8q24
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Funding
- CREST, Japan Science and Technology Agency (JST)
- Funding Program for Next Generation World-Leading Researchers [LS094]
- Japan Society for the Promotion of Science (JSPS) [25861199]
- Grants-in-Aid for Scientific Research [25861199, 25430111] Funding Source: KAKEN
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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-beta 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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