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

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. (Cancer Sci 2011; 102: 245-252)

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage

“…Recent studies have indicated that lncRNAs are transcribed from cancer risk loci and that these transcripts can play important roles in tumorigenesis. [30][31][32] Here, we used RNA-seq to identify two estrogenregulated lncRNAs (CUPID1 and CUPID2) that might contribute to the risk of developing breast cancer by modulating pathway choice of DSB repair.…”

Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence

“…One of the overexpressed lncRNAs in prostate cancer, PCGEM1, is tissue specific and PCa-associated lncRNA gene (15), whereas another highly expressed lncRNA, PRNCR1 (PCAT8), is pervasively transcribed from the critical region of 8q24 Region 2, which is significantly associated with PCa susceptibility (17). Previous studies also demonstrated that a novel long non-coding RNA (named PlncRNA-1) was frequently overexpressed in PCa cell lines and tissues and associated with cell viability and cell apoptosis (18).…”

The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine

“…HULC, for example, is highly expressed in HCC and in colorectal carcinomas that metastasized to the liver, 96,105 but not in the primary colon tumors or in non-liver metastases, whereas other three lncRNAs, PCGEM1, DD3 and PRNCR1, have been associated solely with prostate cancer. 102,[106][107][108][109] Another tissue-specific lncRNA is papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3), which is thyroid specific and downregulated in tumor tissue compared with unaffected thyroid tissue. 110 A key goal for future progress is to identify lncRNAs that could potentially serve as biomarkers for specific disease states.…”

“…101 A novel lncRNA termed 'PRNCR1' (prostate cancer non-coding RNA 1) is upregulated in some of the prostate cancer cells as well as precursor lesion prostatic intraepithelial neoplasia, knockdown of PRNCR1 can attenuate the viability of PC cells and the transactivation activity of the androgen receptor. 102 Although our understanding of the molecular mechanisms of lncRNA function is limited, some features of lncRNAs, including structural scaffolds for protein complexes and complex RNA structural motifs, make them ideal candidates for therapeutic intervention. 103 Preventing the interactions of HOTAIR with the PRC2 or LSD1 complexes, by targeting endogenous HOTAIR and/or using small molecular inhibitors of PRC2, for example, may limit the metastatic potential of breast cancer.…”