Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers.
Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers.
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DOI：
10.1038/bjc.2013.698
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发表时间：
2014-01-07
影响因子：
8.8
通讯作者：
Mimori, K.
中科院分区：
文献类型：
--
作者：
Takahashi, Y.;Sawada, G.;Kurashige, J.;Uchi, R.;Matsumura, T.;Ueo, H.;Takano, Y.;Eguchi, H.;Sudo, T.;Sugimachi, K.;Yamamoto, H.;Doki, Y.;Mori, M.;Mimori, K.
我们先前进行了基因表达微阵列分析，以确定结直肠癌（CRC）转移和预后的新指标，从中我们确定PVT-1作为候选基因。PVT-1编码一个长的非编码RNA，定位于染色体8 q24，其拷贝数扩增是多种恶性疾病中最常见的事件之一。然而，PVT-1的分子作用机制仍不清楚。我们使用用PVT-1 siRNA或阴性对照siRNA转染的结直肠癌细胞系进行细胞增殖和侵袭测定。对这些细胞系进行基因表达微阵列分析，以研究PVT-1的分子功能。此外，我们通过qRT-PCR研究了PVT-1表达对164例结直肠癌患者预后的影响。用PVT-1 siRNA转染的CRC细胞表现出其增殖和侵袭能力的显著丧失。在这些细胞中，TGF-β信号通路和凋亡信号被显著激活。此外，单因素和多因素分析显示，PVT-1表达水平是结直肠癌患者总生存率的独立危险因素。定位于8 q24的PVT-1在CRC中产生抗凋亡活性，并且PVT-1的异常表达是CRC患者的预后指标。
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.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
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影响因子：
64.5
作者：
Rinn, John L.;Kertesz, Michael;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
16.8
作者：
Espinoza, CA;Allen, TA;Goodrich, JA
通讯作者：
Goodrich, JA
影响因子：
16
作者：
Mariner, Peter D.;Walters, Ryan D.;Goodrich, James A.
通讯作者：
Goodrich, James A.