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Identification of alternative splicing in transcript isoforms in patients with ulcerative colitis: effects of disease duration

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dc.contributor.authorLow, ENDen_US
dc.contributor.authorWong, Zen_US
dc.contributor.authorNgiu, CSen_US
dc.contributor.authorNazefah, AHen_US
dc.contributor.authorRafiz, ARen_US
dc.contributor.authorMokhtar, Nen_US
dc.contributor.authorAli, RARen_US
dc.date.accessioned2024-05-29T02:50:30Z
dc.date.available2024-05-29T02:50:30Z
dc.date.issued2017
dc.descriptionPoster presentationsen_US
dc.description.abstractBackground: Patients with long duration ulcerative colitis (UC) patients have high risk of developing colitis-associated cancer (CAC). Chronic diseases including various types of cancer have been associated with aberrant alternative splicing (AS). However, data on AS in chronic IBD such as UC and CAC is still lacking. Aberrant alternative splicing (AS) has been linked with various types of cancer but its association with CAC has not been well defined. This study aimed to determine the crucial genes that are differentially spliced within the UC susceptibility loci in long duration UC as compared with short duration UC. Methods: To date, a total of 15 patients (11 with short duration <5 years and four with long duration >20 years) were recruited. During routine colonoscopy procedure, the inflammed colonic tissues were biopsied and RNA was extracted and hybridised to the Affymetrix GeneChip® Human Transcriptome Array 2.0. Affymetrix Transcriptome Analysis Console was used to identify AS events (splicing index>|1.5|, ANOVA p<0.05, false discovery rate<0.05). KOBAS 2.0 was used for KEGG and Gene Ontology analysis. Results: A total of 2,443 genes exhibited differential splicing between long duration UC and short duration UC. Alternate 3' acceptor, alternate 5' donor, cassette exon and intron retention events were reported. Both negative (range −1.51 to −143.98) and positive (range 1.51 to 204.48) splicing indexes were reported. Among these, 11 genes were IBD susceptibility loci (REL, STAT1, ERAP2, TRAF3IP2, PHACTR2, CNTF, VDR, RPS6KB1, CD226, HCK and TNFRSF6b) and three genes were UC-specific (NFKB1, SLC9A3 and HNF4A). The KEGG pathway and Gene Ontology analysis showed enrichment for immune regulatory and CAC pathways (p<0.05). Among all, JAK/STAT signalling pathway was the most prominent pathway which contains genes that were differentially spliced between long duration UC compared to short duration UC. Conclusions: This is the first study that has successfully discovered alternative splicing events in the crucial genes that possibly involved in the transformation of long duration UC to colitis associated cancer. Further validation is essential to confirm the alternative splicing events in order to understand the potential mechanisms in carcinogenesis derived from chronic ulcerative colitis.en_US
dc.identifier.epageS95
dc.identifier.isbn1876-4479
dc.identifier.issn1873-9946
dc.identifier.scopusWOS:000398606900159
dc.identifier.spageS94
dc.identifier.urihttps://oarep.usim.edu.my/handle/123456789/11070
dc.identifier.volume11
dc.languageEnglish
dc.language.isoen_USen_US
dc.publisherOxford Univ Pressen_US
dc.relation.ispartofJournal Of Crohns & Colitisen_US
dc.sourceWeb Of Science (ISI)
dc.titleIdentification of alternative splicing in transcript isoforms in patients with ulcerative colitis: effects of disease durationen_US
dc.typeArticleen_US
dspace.entity.typePublication

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