Targeting the Oncogenic Long Non-coding RNA SLNCR1 by Blocking Its Sequence-Specific Binding to the Androgen Receptor

Schmidt, Karyn; Weidmann, Chase A.; Hilimire, Thomas A.; Yee, Elaine; Hatfield, Breanne M; Schneekloth, John S.; Weeks, Kevin M.; Novina, Carl D.

doi:10.1016/j.celrep.2019.12.011

Cited by 50 publications

(33 citation statements)

References 56 publications

(91 reference statements)

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“…Apart from the most widely adopted methods that we have described, other strategies have emerged to improve the global characterization of ncRNAs in the last 10 years (Table 2) and the optimization of these methods is still ongoing. Notwithstanding, in some cases, it is not possible to completely clarify the function of non-coding transcripts out of a physiological context, especially because are poorly conserved between species, making the in vivo experiments not easily translatable for applications in humans and because, if compared to coding genes, are Is a technique to unravel the secondary structure of lncRNAs [164][165][166] PARS (Parallel analysis of RNA structure) Is a methods able to explore changes in lncRNAs structurome that can occurs in carcinogenesis, recently implemented with the Illumina platform (nextPARS) to provide results with higher throughput and sample multiplexing [167][168][169] Frag-Seq (Fragmentation sequencing) Is an assay for probing RNA structure at transcriptome-wide level by combining RNA-seq and tools determining nuclease accessibility at single base resolution [99,170,171] ICE-seq (Inosine chemical erasing sequencing)…”

Section: Resultsmentioning

confidence: 99%

Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”

Grillone

Riillo

Scionti

et al. 2020

J Exp Clin Cancer Res

147

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The discovery of the role of non-coding RNAs (ncRNAs) in the onset and progression of malignancies is a promising frontier of cancer genetics. It is clear that ncRNAs are candidates for therapeutic intervention, since they may act as biomarkers or key regulators of cancer gene network. Recently, profiling and sequencing of ncRNAs disclosed deep deregulation in human cancers mostly due to aberrant mechanisms of ncRNAs biogenesis, such as amplification, deletion, abnormal epigenetic or transcriptional regulation. Although dysregulated ncRNAs may promote hallmarks of cancer as oncogenes or antagonize them as tumor suppressors, the mechanisms behind these events remain to be clarified. The development of new bioinformatic tools as well as novel molecular technologies is a challenging opportunity to disclose the role of the "dark matter" of the genome. In this review, we focus on currently available platforms, computational analyses and experimental strategies to investigate ncRNAs in cancer. We highlight the differences among experimental approaches aimed to dissect miRNAs and lncRNAs, which are the most studied ncRNAs. These two classes indeed need different investigation taking into account their intrinsic characteristics, such as length, structures and also the interacting molecules. Finally, we discuss the relevance of ncRNAs in clinical practice by considering promises and challenges behind the bench to bedside translation.

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Section: Resultsmentioning

confidence: 99%

Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”

Grillone

Riillo

Scionti

et al. 2020

J Exp Clin Cancer Res

147

View full text Add to dashboard Cite

show abstract

“…Interestingly, several confirmed AR bound lncRNAs, such as HOTAIR , SRA , SLNCR1 , and even PCGEM1 , all include a conserved region with a similar sequence ( SLNCR1 609–637 ) which is required for AR-lncRNA interaction ( Yang et al, 2013 ; Zhang et al, 2015 ; Schmidt et al, 2016 ). Further investigation revealed that AR NTD binds with short, pyrimidine-rich RNA containing at least one CYUYUCCWS motif, and lncRNA HOXA11-AS-203 which contains such motif was validated to bind with AR NTD ( Schmidt et al, 2020 ). These studies strongly suggested that some lncRNAs containing specific sequences may bind to AR protein and other steroid receptors at the DNA binding domain to compete with the target response elements and suppress their transcriptional activity, or at the N-terminal regulatory domain to modulate their transactivation.…”

Section: Ncrnas As Ar Regulatorsmentioning

confidence: 99%

Androgen Receptor-Related Non-coding RNAs in Prostate Cancer

Yang

Liu

et al. 2021

Front. Cell Dev. Biol.

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Prostate cancer (PCa) is the second leading cause of cancer-related death among men in the United States. Androgen receptor (AR) signaling is the dominant oncogenic pathway in PCa and the main strategy of PCa treatment is to control the AR activity. A large number of patients acquire resistance to Androgen deprivation therapy (ADT) due to AR aberrant activation, resulting in castration-resistant prostate cancer (CRPC). Understanding the molecular mechanisms underlying AR signaling in the PCa is critical to identify new therapeutic targets for PCa patients. The recent advances in high-throughput RNA sequencing (RNA-seq) techniques identified an increasing number of non-coding RNAs (ncRNAs) that play critical roles through various mechanisms in different diseases. Some ncRNAs have shown great potentials as biomarkers and therapeutic targets. Many ncRNAs have been investigated to regulate PCa through direct association with AR. In this review, we aim to comprehensively summarize recent findings of the functional roles and molecular mechanisms of AR-related ncRNAs as AR regulators or targets in the progression of PCa.

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“…Adduct formation is dependent on nucleotide flexibility and is quantified at nucleotide resolution by performing RT and comparing the product against a control [ 138 ]. This can be further coupled with mutational profiling (MaP), which accounts for the occasional incorporation of noncomplementary nucleotides or deletions caused by reverse transcriptase enzymes, to generate SHAPE profiles where mutations are counted and facilitate the identification of RNA secondary structure formation at nucleotide resolution [ 139 , 140 ]. With valuable evidence supporting the expression, localisation and possible structure of the target lncRNAs, the next step is to estimate and conclusively identify what biomolecules may be interacting with it.…”

Section: Identification and Primary Characterisationmentioning

confidence: 99%

Approaches to Identify and Characterise the Post-Transcriptional Roles of lncRNAs in Cancer

Carter

Ang

Sim

et al. 2021

ncRNA

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It is becoming increasingly evident that the non-coding genome and transcriptome exert great influence over their coding counterparts through complex molecular interactions. Among non-coding RNAs (ncRNA), long non-coding RNAs (lncRNAs) in particular present increased potential to participate in dysregulation of post-transcriptional processes through both RNA and protein interactions. Since such processes can play key roles in contributing to cancer progression, it is desirable to continue expanding the search for lncRNAs impacting cancer through post-transcriptional mechanisms. The sheer diversity of mechanisms requires diverse resources and methods that have been developed and refined over the past decade. We provide an overview of computational resources as well as proven low-to-high throughput techniques to enable identification and characterisation of lncRNAs in their complex interactive contexts. As more cancer research strategies evolve to explore the non-coding genome and transcriptome, we anticipate this will provide a valuable primer and perspective of how these technologies have matured and will continue to evolve to assist researchers in elucidating post-transcriptional roles of lncRNAs in cancer.

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Targeting the Oncogenic Long Non-coding RNA SLNCR1 by Blocking Its Sequence-Specific Binding to the Androgen Receptor

Cited by 50 publications

References 56 publications

Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”

Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”

Androgen Receptor-Related Non-coding RNAs in Prostate Cancer

Approaches to Identify and Characterise the Post-Transcriptional Roles of lncRNAs in Cancer

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