Abstract
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 × 10-24, OR = 1.74, 95% confidence interval = 1.56-1.93). Importantly, we show that this region was transcribed as a 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.
| Original language | English |
|---|---|
| Pages (from-to) | 245-252 |
| Number of pages | 8 |
| Journal | Cancer Science |
| Volume | 102 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2011 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
}
Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. / Chung, Suyoun; Nakagawa, Hidewaki; Uemura, Motohide; Piao, Lianhua; Ashikawa, Kyota; Hosono, Naoya; Takata, Ryo; Akamatsu, Shusuke; Kawaguchi, Takahisa; Morizono, Takashi; Tsunoda, Tatsuhiko; Daigo, Yataro; Matsuda, Koichi; Kamatani, Naoyuki; Nakamura, Yusuke; Kubo, Michiaki.
In: Cancer Science, Vol. 102, No. 1, 01.01.2011, p. 245-252.Research output: Contribution to journal › Article
TY - JOUR
T1 - Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility
AU - Chung, Suyoun
AU - Nakagawa, Hidewaki
AU - Uemura, Motohide
AU - Piao, Lianhua
AU - Ashikawa, Kyota
AU - Hosono, Naoya
AU - Takata, Ryo
AU - Akamatsu, Shusuke
AU - Kawaguchi, Takahisa
AU - Morizono, Takashi
AU - Tsunoda, Tatsuhiko
AU - Daigo, Yataro
AU - Matsuda, Koichi
AU - Kamatani, Naoyuki
AU - Nakamura, Yusuke
AU - Kubo, Michiaki
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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 × 10-24, OR = 1.74, 95% confidence interval = 1.56-1.93). Importantly, we show that this region was transcribed as a 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.
AB - 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 × 10-24, OR = 1.74, 95% confidence interval = 1.56-1.93). Importantly, we show that this region was transcribed as a 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.
UR - http://www.scopus.com/inward/record.url?scp=78650200618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650200618&partnerID=8YFLogxK
U2 - 10.1111/j.1349-7006.2010.01737.x
DO - 10.1111/j.1349-7006.2010.01737.x
M3 - Article
VL - 102
SP - 245
EP - 252
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 1
ER -