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PROSTATE CANCER-ASSOCIATED NONCODING RNA 1; PRNCR1

PROSTATE CANCER-ASSOCIATED NONCODING RNA 1; PRNCR1

Alternative titles; symbolsPROSTATE CANCER-ASSOCIATED TRANSCRIPT 8; PCAT8CANCER-ASSOCIATED REGION LONG NONCODING RNA 4; CARLO3lncRNA CARLO3HGNC Approved Gene Sym...

Alternative titles; symbols

  • PROSTATE CANCER-ASSOCIATED TRANSCRIPT 8; PCAT8
  • CANCER-ASSOCIATED REGION LONG NONCODING RNA 4; CARLO3
  • lncRNA CARLO3

HGNC Approved Gene Symbol: PRNCR1

Cytogenetic location: 8q24.21 Genomic coordinates (GRCh38): 8:127,079,873-127,092,594 (from NCBI)

▼ Description
Long noncoding RNAs (lncRNAs), such as PRNCR1, are transcripts longer than 200 bp that have no protein-coding potential and function in various cellular processes (Kim et al., 2014).

▼ Cloning and Expression
By fine mapping and sequencing of a region of chromosome 8 linked with prostate cancer (see HPC10, 611100), Chung et al. (2011) identified PRNCR1. The transcript was approximately 13 kb long and was polyadenylated. PRNCR1 shares sequence similarity with the SRRM1 (605975) transcript from chromosome 1.

By sequence analysis and RACE with human colorectal cancer-derived cells, Kim et al. (2014) identified several lncRNAs, including PRNCR1, which they called CARLO3, in a region of chromosome 8q24.21 that harbors cancer-associated variants and enhancer activity.

▼ Gene Structure
Chung et al. (2011) observed that the PRNCR1 transcript contains no introns.

▼ Mapping
By genomic sequence analysis, Chung et al. (2011) mapped the PRNCR1 gene to chromosome 8q24.

By sequence analysis, Kim et al. (2014) mapped the PRNCR1 gene to a region of chromosome 8q24.21 that lacks protein-coding genes.

▼ Gene Function
Using real-time quantitative RT-PCR, Chung et al. (2011) found that expression of PRNCR1 was upregulated in 5 of 10 microdissected prostate cancer cell populations and 2 of 4 prostate intraepithelial neoplasias compared with normal prostate epithelial cells microdissected from the same prostate cancer tissues. Knockdown of PRNCR1 via small interfering RNA duplexes reduced cell viability in androgen-sensitive LNCaP prostate cancer cells and reduced growth in an androgen receptor (AR; 313700)-negative prostate cancer cell line. Knockdown of PRNCR1 reduced expression of a cotransfected AR reporter gene following androgen stimulation.

Yang et al. (2013) reported that 2 lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 and PCGEM1 (605443), bind successively to the AR and strongly enhance both ligand-dependent and ligand-independent AR-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the carboxy-terminally acetylated AR on enhancers and its association with DOT1L (607375) appear to be required for recruitment of the second lncRNA, PCGEM1, to the AR amino terminus, which is methylated by DOT1L. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited pygopus-2 (PYGO2; 606903) PHD domain enhances selective looping of AR-bound enhancers to target gene promoters in these cells. In resistant prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full-length AR, causing ligand-independent activation of the AR transcriptional program and cell proliferation. Conditionally expressed short hairpin RNA targeting these lncRNAs in castration-resistant prostate cancer cell lines strongly suppressed tumor xenograft growth in vivo. Yang et al. (2013) concluded that these overexpressed lncRNAs can potentially serve as a required component of castration resistance in prostatic tumors.

▼ Molecular Genetics
Chung et al. (2011) identified a 4-SNP haplotype within the PRNCR1 gene that was associated with prostate cancer susceptibility (p = 2.00 x 10(-24), OR = 1.74, 95% confidence interval = 1.56-1.93). For discussion of multiple independent variants on chromosome 8q24 associated with prostate cancer, see HPC10 (611100).

Tags: 8q24.21