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

2013; Springer Nature; Volume: 110; Issue: 1 Linguagem: Inglês

10.1038/bjc.2013.698

1532-1827

Yusuke Takahashi, Genta Sawada, Jyunji Kurashige, Ryutaro Uchi, Tae Matsumura, Ueo H, Yuki Takano, Hidetoshi Eguchi, Tomoya Sudo, K Sugimachi, Hirofumi Yamamoto, Yuichiro� Doki, Masaki Mori, Koshi Mimori,

RNA Research and Splicing

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. 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. 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. PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.