Alternative Splicing of Pre-mRNA in Cancer

Körner, Meike; Miller, Laurence J.

doi:10.2353/ajpath.2009.081135

Cited by 25 publications

(7 citation statements)

References 83 publications

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“…Moreover, in specific tissues, such as airway smooth muscle, GPCRs are expressed extensively and are frequently alternative spliced to create a highly diversified receptor milieu [ 41 ]. Although identification and characterization of alternative spliced genes within GPCR superfamily has not been delineated, it is widely accepted that AS is common in this family and influenced by changing patho-physiological conditions [ 38 , 42 ]. In S .…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Bioinformatical Analysis of Vertebrate Stages of Schistosoma japonicum Reveals Alternative Splicing Events

Zhang

et al. 2015

PLoS ONE

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Alternative splicing is a molecular process that contributes greatly to the diversification of proteome and to gene functions. Understanding the mechanisms of stage-specific alternative splicing can provide a better understanding of the development of eukaryotes and the functions of different genes. Schistosoma japonicum is an infectious blood-dwelling trematode with a complex lifecycle that causes the tropical disease schistosomiasis. In this study, we analyzed the transcriptome of Schistosoma japonicum to discover alternative splicing events in this parasite, by applying RNA-seq to cDNA library of adults and schistosomula. Results were validated by RT-PCR and sequencing. We found 11,623 alternative splicing events among 7,099 protein encoding genes and average proportion of alternative splicing events per gene was 42.14%. We showed that exon skip is the most common type of alternative splicing events as found in high eukaryotes, whereas intron retention is the least common alternative splicing type. According to intron boundary analysis, the parasite possesses same intron boundaries as other organisms, namely the classic “GT-AG” rule. And in alternative spliced introns or exons, this rule is less strict. And we have attempted to detect alternative splicing events in genes encoding proteins with signal peptides and transmembrane helices, suggesting that alternative splicing could change subcellular locations of specific gene products. Our results indicate that alternative splicing is prevalent in this parasitic worm, and that the worm is close to its hosts. The revealed secretome involved in alternative splicing implies new perspective into understanding interaction between the parasite and its host.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Bioinformatical Analysis of Vertebrate Stages of Schistosoma japonicum Reveals Alternative Splicing Events

Zhang

et al. 2015

PLoS ONE

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“…(1, 2) Previous studies have shown that some cancers express increased transcript variants due to alternative splicing events. (3, 4) We hypothesized that alternative splicing might be one of the mechanisms by which dysregulation occurs in cancer, which may result in the oncogenic transformation of cells (altered cell proliferation, apoptosis, invasion, and migration). To explore this hypothesis, our group has recently performed a whole-genome evaluation of ASEs in Head and Neck Squamous Cell Carcinoma (HNSCC), a disease that is characterized by abundant gene expression dysregulation.…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma

Kelley

Flam

Guo

et al. 2018

Translational Research

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We have recently performed the characterization of alternative splicing events (ASEs) in head and neck squamous cell carcinoma, which allows dysregulation of protein expression common for cancer cells. Such analysis demonstrated a high ASE prevalence among tumor samples, including tumor-specific alternative splicing in the GSN gene.In vitro studies confirmed that overall expression of either ASE-GSN or wild-type GSN (WT-GSN) isoform inversely correlated with cell proliferation, whereas the high ratio of ASE-GSN to WT-GSN correlated with increased cellular invasion. Additionally, a change in expression of either isoform caused compensatory changes in expression of the other isoform. Our results suggest that the overall expression and the balance between GSN isoforms are mediating factors in proliferation, while increased overall expression of ASE-GSN is specific to cancer tissues. As a result, we propose ASE-GSN can serve not only as a biomarker of disease and disease progression, but also as a neoantigen for head and neck squamous cell carcinoma treatment, for which only a limited number of disease-specific targeted therapies currently exist.

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“…As with miRNAs, many diseases, including cancer, can be linked to aberrant splicing or the presence of unwanted gene isoforms. 10,11 In this study, we investigate the inhibition of a specific miRNA, miR-155, which is one of the first identified miRNA oncogenes, as well as the spliceshifting of Mcl-1, which is a member of the Bcl-2 family that has both anti-apoptotic and pro-apoptotic isoforms. [12][13][14] Only a few prior studies describe the encapsulation of either PMOs or PNAs into nanoscale delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Polymer Nanoparticle-Mediated Delivery of MicroRNA Inhibition and Alternative Splicing

Cheng

Saltzman

2012

Mol. Pharmaceutics

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The crux of current RNA-based therapeutics relies on association of synthetic nucleic acids with cellular RNA targets. Antisense oligonucleotide binding to mature microRNA and splicing junctions on pre-mRNA represent methods of gene therapy that respectively inhibit microRNA-mediated gene regulation and induce alternative splicing. We have developed biodegradable polymer nanoparticles--which are coated with cell-penetrating peptides--that can effectively deliver chemically-modified oligonucleotide analogs to achieve these forms of gene regulation. We found that this nanoparticle system could block the activity of the oncogenic microRNA, miR-155, as well as modulate splicing to attenuate the expression of the proto-oncogene, MCL-1. Regulation of these genes in human cancer cells reduced cell viability and produced pro-apoptotic effects. These findings establish polymer nanoparticles as delivery vectors for non-conventional forms of gene therapy activated by cellular delivery of RNA-targeted molecules, which have strong therapeutic implications.

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Alternative Splicing of Pre-mRNA in Cancer

Cited by 25 publications

References 83 publications

Transcriptome Bioinformatical Analysis of Vertebrate Stages of Schistosoma japonicum Reveals Alternative Splicing Events

Transcriptome Bioinformatical Analysis of Vertebrate Stages of Schistosoma japonicum Reveals Alternative Splicing Events

Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma

Polymer Nanoparticle-Mediated Delivery of MicroRNA Inhibition and Alternative Splicing

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