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 |
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Format: | Artikel |
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. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/bjc.2013.698 |