Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays

Cheung, Hannah; Baggerly, Keith A.; Tsavachidis, Spiridon; Bachinski, Linda L.; Neubauer, Valerie L.; Nixon, Tamara J.; Aldape, Kenneth; Cote, Gilbert J.; Krahe, Ralf

doi:10.1186/1471-2164-9-216

Cited by 64 publications

(74 citation statements)

References 46 publications

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“…Recent studies suggest A2BP1 may also contribute to several other human diseases, including cancer, autism and osteoarthritis (Cheung et al, 2008;Huang et al, 2009;Martin et al, 2007;Zhai et al, 2009). Previous molecular analysis of mammalian A2BP1 has focused on its role in alternative splicing (Auweter et al, 2006;Fukumura et al, 2009;Jin et al, 2003;Kuroyanagi et al, 2007;Lee et al, 2009;Minovitsky et al, 2005;Nakahata and Kawamoto, 2005;Underwood et al, 2005;Zhang et al, 2008;Zhou et al, 2007;Zhou and Lou, 2008).…”

Section: Research Articlementioning

confidence: 99%

DrosophilaAtaxin 2-binding protein 1 marks an intermediate step in the molecular differentiation of female germline cysts

Tastan

Maines

et al. 2010

Development

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SUMMARYIn the Drosophila ovary, extrinsic signaling from the niche and intrinsic translational control machinery regulate the balance between germline stem cell maintenance and the differentiation of their daughters. However, the molecules that promote the continued stepwise development of ovarian germ cells after their exit from the niche remain largely unknown. Here, we report that the early development of germline cysts depends on the Drosophila homolog of the human ataxin 2-binding protein 1 (A2BP1) gene. Drosophila A2BP1 protein expression is first observed in the cytoplasm of 4-, 8-and 16-cell cysts, bridging the expression of the early differentiation factor Bam with late markers such as Orb, Rbp9 and Bruno encoded by arrest. The expression of A2BP1 is lost in bam, sans-fille (snf) and mei-P26 mutants, but is still present in other mutants such as rbp9 and arrest. A2BP1 alleles of varying strength produce mutant phenotypes that include germline counting defects and cystic tumors. Phenotypic analysis reveals that strong A2BP1 alleles disrupt the transition from mitosis to meiosis. These mutant cells continue to express high levels of mitotic cyclins and fail to express markers of terminal differentiation. Biochemical analysis reveals that A2BP1 isoforms bind to each other and associate with Bruno, a known translational repressor protein. These data show that A2BP1 promotes the molecular differentiation of ovarian germline cysts.

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Section: Research Articlementioning

confidence: 99%

DrosophilaAtaxin 2-binding protein 1 marks an intermediate step in the molecular differentiation of female germline cysts

Tastan

Maines

et al. 2010

Development

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“…GSE4290 provided the largest data set for a comparison containing 23 samples from epilepsy patients used as nontumor samples and 81 grade 4 adult GBM samples (17). Expression and clustering analyses were done as described previously (12). We used probe sets described previously as segregating nontumor from tumor samples based on known functions in general and alternative splicing, RNA export, RNA degradation, miRNA processing, and nonsense-mediated decay (12).…”

Section: Analysis Of Yb-1 Expression In Adult Glioblastomamentioning

confidence: 99%

“…Expression and clustering analyses were done as described previously (12). We used probe sets described previously as segregating nontumor from tumor samples based on known functions in general and alternative splicing, RNA export, RNA degradation, miRNA processing, and nonsense-mediated decay (12). Hierarchical clustering was done with the EBI Profiler tool decreased the average number difference of the colonies formed compared with the control.…”

Section: Analysis Of Yb-1 Expression In Adult Glioblastomamentioning

confidence: 99%

“…This is because YB-1 facilitates viral replication and therefore can be used for gene therapy approaches. YB-1, also called nuclease-sensitive element binding protein 1 (NSEP1), is among the top genes that are differentially expressed in pediatric glioblastoma, as well as in adult glioblastoma, when compared with control brain tissues (11,12). YB-1 is detectable in 100% (14 of 14 cases) of primary pediatric glioblastoma tumor tissues based on quantitative reverse transcription-PCR, whereas at the protein level it is detectable in 81% (26 of 32 cases) of tumors at high levels (2,11).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase

Gao

Fotovati

Lee

et al. 2009

Molecular Cancer Therapeutics

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Glioblastoma multiforme (GBM) is an aggressive type of brain tumor where <3% of newly diagnosed cases in the patients will survive >5 years. In adults, GBM is the most common type of brain tumor. It is rarer in children, where it constitutes ∼15% of all brain tumors diagnosed. These tumors are often invasive, making surgical resection difficult. Further, they can be refractory to current therapies such as temozolomide. The current dogma is that temozolomide resistance rests on the expression of O 6 -methylguanine-DNA methyltransferase (MGMT) because it cleaves methylated DNA adducts formed by the drug. Our laboratory recently reported that another drug resistance gene known as the Y-box binding protein-1 (YB-1) is highly expressed in primary GBM but not in normal brain tissues based on the evaluation of primary tumors. We therefore questioned whether GBM depend on YB-1 for growth and/or response to temozolomide. Herein, we report that YB-1 inhibition reduced tumor cell invasion and growth in monolayer as well as in soft agar. Moreover, blocking this protein ultimately delayed tumor onset in mice. Importantly, inhibiting YB-1 enhanced temozolomide sensitivity in a manner that was independent of MGMT in models of adult and pediatric GBM. In conclusion, inhibiting YB-1 may be a novel way to improve the treatment of GBM. [Mol Cancer Ther 2009;8(12):3276-84]

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“…The pace of mRNA processing research has increased following the introduction of new genome-wide approaches to the study of alternative mRNA processing Venables et al 2009;Pickrell et al 2010), and has been particularly invigorated following the commercial availability of splice-sensitive microarrays such as the Affymetrix Human Exon 1.0 ST array (HuEx) (Gardina et al 2006;Cheung et al 2008;Thorsen et al 2008;Xi et al 2008). The data generated by these genome-wide transcript assays have been accompanied by a number of analytical approaches and software (Affymetrix 2005;Cline et al 2005;Sandberg et al 2008;Xing et al 2008;Laajala et al 2009).…”

Section: Introductionmentioning

confidence: 99%

SplicerEX: A tool for the automated detection and classification of mRNA changes from conventional and splice-sensitive microarray expression data

Robinson

Forte

Salinas

et al. 2012

RNA

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The key postulate that one gene encodes one protein has been overhauled with the discovery that one gene can generate multiple RNA transcripts through alternative mRNA processing. In this study, we describe SplicerEX, a novel and uniquely motivated algorithm designed for experimental biologists that (1) detects widespread changes in mRNA isoforms from both conventional and splice sensitive microarray data, (2) automatically categorizes mechanistic changes in mRNA processing, and (3) mitigates known technological artifacts of exon array-based detection of alternative splicing resulting from 59 and 39 signal attenuation, background detection limits, and saturation of probe set signal intensity. In this study, we used SplicerEX to compare conventional and exon-based Affymetrix microarray data in a model of EBV transformation of primary human B cells. We demonstrated superior detection of 39-located changes in mRNA processing by the Affymetrix U133 GeneChip relative to the Human Exon Array. SplicerEX-identified exon-level changes in the EBV infection model were confirmed by RT-PCR and revealed a novel set of EBV-regulated mRNA isoform changes in caspases 6, 7, and 8. Finally, SplicerEX as compared with MiDAS analysis of publicly available microarray data provided more efficiently categorized mRNA isoform changes with a significantly higher proportion of hits supported by previously annotated alternative processing events. Therefore, SplicerEX provides an important tool for the biologist interested in studying changes in mRNA isoform usage from conventional or splicesensitive microarray platforms, especially considering the expansive amount of archival microarray data generated over the past decade. SplicerEX is freely available upon request.

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Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays

Cited by 64 publications

References 46 publications

DrosophilaAtaxin 2-binding protein 1 marks an intermediate step in the molecular differentiation of female germline cysts

DrosophilaAtaxin 2-binding protein 1 marks an intermediate step in the molecular differentiation of female germline cysts

Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase

SplicerEX: A tool for the automated detection and classification of mRNA changes from conventional and splice-sensitive microarray expression data

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