Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility

被引：229

作者：

Chung, Suyoun ^{[1
]}

Nakagawa, Hidewaki ^{[1
,2
]}

Uemura, Motohide ^{[1
]}

Piao, Lianhua ^{[1
]}

Ashikawa, Kyota ^{[3
]}

Hosono, Naoya ^{[3
]}

Takata, Ryo ^{[2
]}

Akamatsu, Shusuke ^{[2
]}

Kawaguchi, Takahisa ^{[4
]}

Morizono, Takashi ^{[4
]}

Tsunoda, Tatsuhiko ^{[4
]}

Daigo, Yataro ^{[1
]}

Matsuda, Koichi ^{[1
]}

Kamatani, Naoyuki ^{[5
]}

Nakamura, Yusuke ^{[1
]}

Kubo, Michiaki ^{[3
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Mol Med Lab, Ctr Human Genome, Tokyo, Japan

[2] RIKEN, Ctr Genom Med, Lab Biomarker Dev, Yokohama, Kanagawa, Japan

[3] RIKEN, Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[4] RIKEN, Ctr Genom Med, Lab Med Informat, Yokohama, Kanagawa, Japan

[5] RIKEN, Ctr Genom Med, Lab Stat Anal, Yokohama, Kanagawa, Japan

来源：

CANCER SCIENCE | 2011年 / 102卷 / 01期

基金：

日本学术振兴会;

关键词：

GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER; CHROMOSOME; 8Q24; RISK LOCUS; GENE-EXPRESSION; MESSENGER-RNA; MULTIPLE LOCI; VARIANT; COMPLEX; IDENTIFICATION;

D O I：

10.1111/j.1349-7006.2010.01737.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent genome-wide association studies reported strong and reproducible associations of multiple genetic variants in a large "gene-desert" region of chromosome 8q24 with susceptibility to prostate cancer (PC). However, the causative or functional variants of these 8q24 loci and their biological mechanisms associated with PC susceptibility remain unclear and should be investigated. Here, focusing on its most centromeric region (so-called Region 2: Chr8: 128.14-128.28 Mb) among the multiple PC loci on 8q24, we performed fine mapping and re-sequencing of this critical region and identified SNPs (single nucleotide polymorphisms) between rs1456315 and rs7463708 (chr8: 128,173,119-128,173,237 bp) to be most significantly associated with PC susceptibility (P = 2.00 x 10-24, OR = 1.74, 95% confidence interval = 1.56-1.93). Importantly, we show that this region was transcribed as a similar to 13 kb intron-less long non-coding RNA (ncRNA), termed PRNCR1 (prostate cancer non-coding RNA 1), and PRNCR1 expression was upregulated in some of the PC cells as well as precursor lesion prostatic intraepithelial neoplasia. Knockdown of PRNCR1 by siRNA attenuated the viability of PC cells and the transactivation activity of androgen receptor, which indicates that PRNCR1 could be involved in prostate carcinogenesis possibly through androgen receptor activity. These findings could provide a new insight in understanding the pathogenesis of genetic factors for PC susceptibility and prostate carcinogenesis. (Cancer Sci 2011; 102: 245-252).

引用

页码：245 / 252

页数：8

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