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Molecular Cancer

, 12:13

First Online: 14 February 2013Received: 07 September 2012Accepted: 11 February 2013DOI: 10.1186-1476-4598-12-13

Cite this article as: Hudson, R.S., Yi, M., Volfovsky, N. et al. Mol Cancer 2013 12: 13. doi:10.1186-1476-4598-12-13

Abstract

BackgroundUltraconserved regions UCR are genomic segments of more than 200 base pairs that are evolutionarily conserved among mammalian species. They are thought to have functions as transcriptional enhancers and regulators of alternative splicing. Recently, it was shown that numerous RNAs are transcribed from these regions. These UCR-encoded transcripts ucRNAs were found to be expressed in a tissue- and disease-specific manner and may interfere with the function of other RNAs through RNA: RNA interactions. We hypothesized that ucRNAs have unidentified roles in the pathogenesis of human prostate cancer. In a pilot study, we examined ucRNA expression profiles in human prostate tumors.

MethodsUsing a custom microarray with 962 probesets representing sense and antisense sequences for the 481 human UCRs, we examined ucRNA expression in resected, fresh-frozen human prostate tissues 57 tumors, 7 non-cancerous prostate tissues and in cultured prostate cancer cells treated with either epigenetic drugs the hypomethylating agent, 5-Aza 2deoxycytidine, and the histone deacetylase inhibitor, trichostatin A or a synthetic androgen, R1881. Expression of selected ucRNAs was also assessed by qRT-PCR and NanoString®-based assays. Because ucRNAs may function as RNAs that target protein-coding genes through direct and inhibitory RNA: RNA interactions, computational analyses were applied to identify candidate ucRNA:mRNA binding pairs.

ResultsWe observed altered ucRNA expression in prostate cancer e.g., uc.106+, uc.477+, uc.363 + A, uc.454 + A and found that these ucRNAs were associated with cancer development, Gleason score, and extraprostatic extension after controlling for false discovery false discovery rate < 5% for many of the transcripts. We also identified several ucRNAs that were responsive to treatment with either epigenetic drugs or androgen R1881. For example, experiments with LNCaP human prostate cancer cells showed that uc.287+ is induced by R1881 P < 0.05 whereas uc.283 + A was up-regulated following treatment with combined 5-Aza 2deoxycytidine and trichostatin A P < 0.05. Additional computational analyses predicted RNA loop-loop interactions of 302 different sense and antisense ucRNAs with 1058 different mRNAs, inferring possible functions of ucRNAs via direct interactions with mRNAs.

ConclusionsThis first study of ucRNA expression in human prostate cancer indicates an altered transcript expression in the disease.

KeywordsUltraconserved region Gene expression Prostate cancer AbbreviationsUCRUltraconserved regions

miRmicroRNA

ucRNAUCR-encoded transcript

EPEExtraprostatic disease extension

FDRFalse discovery rate.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-12-13 contains supplementary material, which is available to authorized users.

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Autor: Robert S Hudson - Ming Yi - Natalia Volfovsky - Robyn L Prueitt - Dominic Esposito - Stefano Volinia - Chang-Gong Liu - A

Fuente: https://link.springer.com/



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