Alternative splicing in cancer: implications for biology and therapy

Chen, J; Weiss, William A.

doi:10.1038/onc.2013.570

Cited by 250 publications

(256 citation statements)

References 168 publications

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“…72 During tumorigenesis, RNA splicing may bias toward oncogenic SVs to support cancer initiation and progression. 73 Alternative splicing occurs in 95% of multi-exon genes 73 and, in a small minority of cases, may be influenced by L1, resulting in transcriptional interference. The L1 sequence contains polyadenylation sites as well as donor and acceptor splice sites that may induce novel alternative splicing via retention, exonization, or polyadenylation of the upstream intronic sequences.…”

Section: Functions Of L1s In Cancer Retrotransposition-dependent Funcmentioning

confidence: 99%

LINE-1 in cancer: multifaceted functions and potential clinical implications

Han

et al. 2016

Genetics in Medicine

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ReviewThe human genome is abundant with interspersed repetitive sequences originated from retrotransposons. Until now, three categories of retrotransposons have remained unequivocally active: LINE-1(L1), Alu, and SVA elements. The first one is autonomous-capable of self-propagation through RNA intermediates-and the latter two are nonautonomous and thus rely on L1 for mobilization. There are approximately 500,000 L1 copies in the human genome, composing 17% of human DNA.

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Section: Functions Of L1s In Cancer Retrotransposition-dependent Funcmentioning

confidence: 99%

LINE-1 in cancer: multifaceted functions and potential clinical implications

Han

et al. 2016

Genetics in Medicine

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“…An increasing amount of literature in the last years shows involvement of splicing in cancer and an incredible number of splice variants have been described to be associated with tumour progression -for recent reviews see [9,13,14] . For example, epidermal growth factor receptor, which is mutated in several cancers, has a splice variant that is missing exon 4 and is highly expressed in several cancers; this exon deletion makes the protein constitutively active [15] .…”

Section: As In Cancer -Associated Noise or Causality?mentioning

confidence: 99%

Modulators of alternative splicing as novel therapeutics in cancer

Oltean¹

2015

WJCO

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have now conclusively shown that more than 90% of genes are alternatively spliced in humans. This makes AS one of the main drivers of proteomic diversity and, consequently, determinant of cellular function repertoire. Unsurprisingly, given its extent, numerous splice isoforms have been described to be associated with several dise ases including cancer. Many of them have antagonistic functions, e.g. , pro and antiangiogenic or pro and antiapoptotic. Additionally several splice factors have been recently described to have oncogene or tumour suppressors activities, like SF3B1 which is frequently mutated in myelodysplastic syndromes. Beside the implications for cancer pathogenesis, deregulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Approaches involving the use of oligonucleotides as well as small molecule splicing modulators are presented as well as thoughts on how specificity might be accomplished in splicing therapeutics. Core tip: Genomewide studies have recently shown that more than 90% of genes are alternatively spliced in humans. This makes alternative splicing (AS) one of the main drivers of proteomic diversity. Numerous splice isoforms have been described to be associated with cancer. Additionally several splice factors have been shown to have oncogene or tumour suppressors activities. Beside the implications for cancer pathogenesis, deregulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Modulators of alternative splicing as novel therapeutics in cancer AbstractAlternative splicing (AS), the process of removing introns from premRNA and rearrangement of exons to give several types of mature transcripts, has been described more than 40 years ago. However, until recently, it has not been clear how extensive it is. Genomewide studies

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“…The process is catalyzed by the spliceosome and is regulated by the serine/arginine rich (SR) family of proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs). 16 Furthermore, tissue specificity of alternative splicing is mediated by tissue related splicing factors and their posttranslational modification like phosphorylation. 17 Tn-C alternative splicing seems to be cell cycle dependent and epigenetically regulated by extracellular pH at least in normal nonmalignant cells.…”

Section: Tenascin-c and Alternative Splicingmentioning

confidence: 99%