Trends in Molecular Medicine
ReviewLong noncoding RNAs and prostate carcinogenesis: the missing ‘linc’?
Section snippets
The emergence of lncRNAs in cancer cell biology
Recent advances in next-generation sequencing technologies have greatly enhanced our understanding of the human transcriptome, and it has been determined that over 90% of the genome is actively transcribed 1, 2. Yet, only a minority of transcripts are translated into proteins. The noncoding portion, initially thought of as the ‘dark matter’ of the genome, thus represents a significant majority of transcriptional output. Noncoding RNAs (ncRNAs) are broadly divided into short (<200 nt) and long
Function 1: lncRNAs as mediators of enhancer-promoter looping in PCa
The androgen receptor (AR; see Glossary) is a transcription factor that is fundamental for growth and survival of prostate cells and thus has a key role in prostate carcinogenesis. AR blockade almost always induces tumor regression and is the first-line treatment for disseminated disease. However, castration-resistant PCa (CRPC) invariably develops and represents the lethal stage of the disease. There is therefore much interest in understanding the mechanisms underlying progression to
Risk prediction: lncRNAs in key PCa susceptibility zone 8q24
Genome-wide association studies have identified a large proportion of cancer-associated genetic variants or single-nucleotide polymorphisms (SNPs) that map to noncoding genomic intervals [53]. Many of these noncoding SNPs are located within enhancers; however, others are found to reside within nc-genes [54]. An analysis of 33 SNPs that are independently associated with PCa risk in European populations identified eight SNPs that localize to lnc-genes, suggesting a possible enrichment of
Concluding remarks and future perspectives
The field of lncRNA cancer biology is undoubtedly only just beginning. There is strong evidence of a major role for lncRNAs in PCa, with several hundred lncRNAs already identified as being aberrantly expressed. The challenge now and in the future is to tease out the truly oncogenic, functionally relevant lncRNAs. Only in doing this can the true biologic significance of lncRNAs in PCa carcinogenesis be realized. Some of the most illuminating findings to come will surely be in our greater
Acknowledgments
We gratefully acknowledge funding from the Irish Cancer Society, the Prostate Cancer Foundation, the Health Research Board, and Movember.
Glossary
- Androgen receptor (AR)
- a member of the steroid-hormone family of nuclear receptors. Upon binding the hormone ligand (testosterone or dihydrotestosterone), the AR dissociates from accessory proteins, translocates to the nucleus, and dimerizes, stimulating transcription of androgen-responsive genes by interacting with an androgen response element (ARE).
- Biochemical recurrence (BCR)
- a rise in prostate-specific antigen (PSA) of ≥0.2 ng/ml following radical prostatectomy, or consecutive rises in PSA
References (82)
microRNAs in cancer management
Lancet Oncol.
(2012)Evolution and functions of long noncoding RNAs
Cell
(2009)- et al.
RNA in the loop
Dev. Cell
(2013) The prostate cancer-up-regulated long noncoding RNA PlncRNA-1 modulates apoptosis and proliferation through reciprocal regulation of androgen receptor
Urol. Oncol.
(2013)The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation
Mol. Cell
(2010)3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA
Cell
(2008)Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer
J. Urol.
(2013)Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a
Mol. Cell
(2010)Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines
Biochim. Biophys. Acta
(2013)Integrative genomic profiling of human prostate cancer
Cancer Cell
(2010)
Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy
Eur. Urol.
Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging
Eur. Urol.
Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer
Eur. Urol.
Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer
Eur. J. Cancer
A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?
Cell
Long noncoding RNAs usher in a new era in the biology of enhancers
Cell
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
Nature
Landscape of transcription in human cells
Nature
MicroRNAs as putative mediators of treatment response in prostate cancer
Nat. Rev. Urol.
The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC
Nat. Struct. Mol. Biol.
Intronic RNAs constitute the major fraction of the non-coding RNA in mammalian cells
BMC Genomics
LNCipedia: a database for annotated human lncRNA transcript sequences and structures
Nucleic Acids Res.
The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression
Genome Res.
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Nature
Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers
Genome Biol.
Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs
Nucleic Acids Res.
Epigenetic regulation by long noncoding RNAs
Science
The functional role of long non-coding RNA in human carcinomas
Mol. Cancer
MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer
Oncogene
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
Nature
Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer
Nat. Struct. Mol. Biol.
Diverse somatic mutation patterns and pathway alterations in human cancers
Nature
Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression
Nat. Biotechnol.
lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs
Nature
PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer
Proc. Natl. Acad. Sci. U.S.A.
Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients
Oncogene
Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility
Cancer Sci.
Gene regulation: Long RNAs wire up cancer growth
Nature
A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
Nature
Activating RNAs associate with Mediator to enhance chromatin architecture and transcription
Nature
RNA processing and its regulation: global insights into biological networks
Nat. Rev. Genet.
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