Alternative <scp>RNA</scp> splicing and cancer

Liu, Sali

doi:10.1002/wrna.1178

Cited by 79 publications

(75 citation statements)

References 226 publications

(271 reference statements)

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“…Furthermore, since regulatory and signaling elements in disordered regions can be comprised of just a few more or less continuous amino acids, and since a high density of functionally important segments can be located within disordered regions, functionality of IDPs can be completely rewired via AS. 266,267 AS is known to occur in almost all human genes, and therefore alterations of this process are intimately connected to the pathogenesis of various human diseases, ranging from cancer, 268,269 to neurodegenerative [270][271][272] and cardiovascular diseases. 273 Many of the pathology-related proteins affected by pathology-related AS are intrinsically disordered.…”

Section: Alternative Splicing In Idp Function and Dysfunctionmentioning

confidence: 99%

Introducing Protein Intrinsic Disorder

et al. 2014

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Section: Alternative Splicing In Idp Function and Dysfunctionmentioning

confidence: 99%

Introducing Protein Intrinsic Disorder

et al. 2014

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“…RNA splicing, the process from nuclear pre-mRNA into mature mRNA where introns are excised and the exons (coding regions) are joined together is mediated by a large complex, called spliceosome or spliceosomal machinery (32,33). In human genome, 60% of the mature mRNAs are spliced by alternative splicing in which pre-mRNAs can be spliced in more than one way (34,35). Alternative splicing tremendously increases the diversity of human transcriptome, resulting in translation of more complex proteome in human.…”

Section: The Spliceosomal Machinery and Rna Splicing Regulationmentioning

confidence: 99%

Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia

Zhou

Chng

2017

Stem Cell Investig.

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The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML). In this article, we describe the diverse roles of aberrant splicing in hematological malignancies, particularly in AML and their contributions to the characteristics of LSC. We review these promising strategies to exploit the addiction of aberrant spliceosomal machinery for anti-leukemic therapy with aim to eradicate LSC. However, given the complexity and plasticity of spliceosome and not fully known functions of splicing in cancer, the challenges facing the development of the therapeutic strategies targeting RAN splicing are highlighted and future directions are discussed too.

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“…The aberrant activation of EMT can be driven by a family of transcription factors, such as the Snail-or Twist-family proteins, and by the cytokine TGFβ. Recent work from our lab has demonstrated that EMT is controlled at the level of alternative RNA splicing, a mechanism that is essential to generate protein diversity (Brown et al, 2011;Liu and Cheng, 2013;Xu et al, 2014). These studies relied on analysis of a crucial cell surface molecule, CD44.…”

Section: Introductionmentioning

confidence: 99%

The CD44s splice isoform is a central mediator for invadopodia activity

Zhao

Wei

et al. 2016

Journal of Cell Science

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The ability for tumor cells to spread and metastasize to distant organs requires proteolytic degradation of extracellular matrix (ECM). This activity is mediated by invadopodia, actin-rich membrane protrusions that are enriched for proteases. However, the mechanisms underlying invadopodia activity are not fully understood. Here, we report that a specific CD44 splice isoform, CD44s, is an integral component in invadopodia. We show that CD44s, but not another splice isoform CD44v, is localized in invadopodia. Small hairpin (sh) RNA-mediated depletion of CD44s abolishes invadopodia activity, prevents matrix degradation and decreases tumor cell invasiveness. Our results suggest that CD44s promotes cortactin phosphorylation and recruits MT1-MMP (also known as MMP14) to sites of matrix degradation, which are important activities for invadopodia function. Importantly, we show that depletion of CD44s inhibits breast cancer cell metastasis to the lung in animals. These findings suggest a crucial mechanism underlying the role of the CD44s splice isoform in breast cancer metastasis.

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Alternative RNA splicing and cancer

Cited by 79 publications

References 226 publications

Introducing Protein Intrinsic Disorder

Introducing Protein Intrinsic Disorder

Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia

The CD44s splice isoform is a central mediator for invadopodia activity

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