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      Identification of long noncoding RNAs with aberrant expression in prostate cancer metastases


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          Prostate cancer (PCa) is the second-most common cause of male cancer-related death in western industrialized countries, and the emergence of metastases is a key challenge in the treatment of PCa. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play an important role in the regulation of diverse cellular and molecular processes during the development and progression of cancer. Here, we utilized a unique cohort of castration-resistant prostate cancer metastases (mCRPC) and corresponding localized tumors and RNA sequencing (RNA-seq). First, we showed that patient-to-patient variability accounted for most of the variance in lncRNA expression between the samples, suggesting that genomic alterations in the samples are the main drivers of lncRNA expression in PCa metastasis. Subsequently, we identified 27 lncRNAs with differential expression (DE-lncRNAs) between metastases and corresponding primary tumors, suggesting that they are mCRPC-specific lncRNAs. Analyses of potential regulation by transcription factors (TFs) revealed that approximately half of the DE-lncRNAs have at least one binding site for the androgen receptor in their regulatory regions. In addition, TF enrichment analysis revealed the enrichment of binding sites for PCa-associated TFs, such as FOXA1 and HOXB13, in the regulatory regions of the DE-lncRNAs. In a cohort of prostatectomy-treated prostate tumors, four of the DE-lncRNAs showed association with progression-free time and two of them (lnc-SCFD2-2 and lnc-R3HCC1L-8) were independent prognostic markers. Our study highlights several mCRPC-specific lncRNAs that might be important in the progression of the disease to the metastatic stage and may also serve as potential biomarkers for aggressive PCa.

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          Long Noncoding RNAs in Cancer Pathways.

          Genome-wide cancer mutation analyses are revealing an extensive landscape of functional mutations within the noncoding genome, with profound effects on the expression of long noncoding RNAs (lncRNAs). While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, we now understand that lncRNAs drive many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein, and RNA. Recent advancements in surveying lncRNA molecular mechanisms are now providing the tools to functionally annotate these cancer-associated transcripts, making these molecules attractive targets for therapeutic intervention in the fight against cancer.
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            Ensembl 2020

            Abstract The Ensembl (https://www.ensembl.org) is a system for generating and distributing genome annotation such as genes, variation, regulation and comparative genomics across the vertebrate subphylum and key model organisms. The Ensembl annotation pipeline is capable of integrating experimental and reference data from multiple providers into a single integrated resource. Here, we present 94 newly annotated and re-annotated genomes, bringing the total number of genomes offered by Ensembl to 227. This represents the single largest expansion of the resource since its inception. We also detail our continued efforts to improve human annotation, developments in our epigenome analysis and display, a new tool for imputing causal genes from genome-wide association studies and visualisation of variation within a 3D protein model. Finally, we present information on our new website. Both software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license) and data updates made available four times a year.
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              Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses.

              Large intergenic noncoding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalog of >8000 human lincRNAs. Our catalog unifies previously existing annotation sources with transcripts we assembled from RNA-seq data collected from ∼4 billion RNA-seq reads across 24 tissues and cell types. We characterize each lincRNA by a panorama of >30 properties, including sequence, structural, transcriptional, and orthology features. We found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that lincRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes. We distinguish an additional subset of transcripts that have high evolutionary conservation but may include short ORFs and may serve as either lincRNAs or small peptides. Our integrated, comprehensive, yet conservative reference catalog of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes.

                Author and article information

                Endocr Relat Cancer
                Endocr Relat Cancer
                Endocrine-Related Cancer
                Bioscientifica Ltd (Bristol )
                03 May 2023
                03 May 2023
                01 August 2023
                : 30
                : 8
                : e220247
                [1 ]Faculty of Medicine and Health Technology , Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland
                [2 ]A.I. Virtanen Institute for Molecular Sciences , University of Eastern Finland, Kuopio, Finland
                [3 ]The James Buchanan Brady Urological Institute , Johns Hopkins School of Medicine, Baltimore, Maryland, USA
                [4 ]Department of Urology , Tampere University Hospital, Tampere, Finland
                [5 ]Foundation for the Finnish Cancer Institute , Helsinki, Finland
                [6 ]Institute of Biomedicine , University of Eastern Finland, Kuopio, Finland
                [7 ]Fimlab Laboratories Ltd , Tampere University Hospital, Tampere, Finland
                Author notes
                Correspondence should be addressed to T Visakorpi: tapio.visakorpi@ 123456tuni.fi
                Author information
                © the author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                : 24 April 2023
                : 03 May 2023

                Oncology & Radiotherapy
                long noncoding rna,metastatic prostate cancer,arcinoma,etastasis,neoplasia
                Oncology & Radiotherapy
                long noncoding rna, metastatic prostate cancer, arcinoma, etastasis, neoplasia


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