title: Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers.
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.
  
  
  CONCLUSIONS
  PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Sawada
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kurashige
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Uchi
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ueo
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sudo
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugimachi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Tsurumihara 4546, Beppu 874-0838, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D018628:Gene Dosage; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015996:Survival Rate; D014162:Transfection
chemical_list: C521123:PVT1 long-non-coding RNA, human; D011506:Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering