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Br J Cancer. 2014 Jan 7;110(1):164-71. doi: 10.1038/bjc.2013.698. Epub 2013 Nov 5.

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

Author information

1
1] Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan [2] Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan.
2
Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
3
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan.

Abstract

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.

PMID:
24196785
PMCID:
PMC3887297
DOI:
10.1038/bjc.2013.698
[Indexed for MEDLINE]
Free PMC Article
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