Please use this identifier to cite or link to this item:
https://doi.org/10.1371/journal.pone.0173772
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dc.title | Chromosome 19q13 disruption alters expressions of CYP2A7, MIA and MIA-RAB4B lncRNA and contributes to FAP-like phenotype in APC mutation-negative familial colorectal cancer patients | |
dc.contributor.author | Thean L.F. | |
dc.contributor.author | Wong Y.H. | |
dc.contributor.author | Lo M. | |
dc.contributor.author | Loi C. | |
dc.contributor.author | Chew M.H. | |
dc.contributor.author | Tang C.L. | |
dc.contributor.author | Cheah P.Y. | |
dc.date.accessioned | 2019-11-01T07:55:01Z | |
dc.date.available | 2019-11-01T07:55:01Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Thean L.F., Wong Y.H., Lo M., Loi C., Chew M.H., Tang C.L., Cheah P.Y. (2017). Chromosome 19q13 disruption alters expressions of CYP2A7, MIA and MIA-RAB4B lncRNA and contributes to FAP-like phenotype in APC mutation-negative familial colorectal cancer patients. PLoS ONE 12 (3) : e0173772. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0173772 | |
dc.identifier.issn | 19326203 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/161204 | |
dc.description.abstract | Familial adenomatous polyposis (FAP) is an autosomal-dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. Our ability to exhaustively screen for APC mutations identify microsatellite-stable and APCmutation negative familial CRC patients, enabling us to search for novel genes. We performed genome-wide scan on two affected siblings of one family and 88 ethnicity- and gender- matched healthy controls to identify deletions shared by the siblings. Combined loss of heterozygosity, copy number and allelic-specific copy number analysis uncovered 5 shared deletions. Long-range polymerase chain reaction (PCR) confirmed chromosome 19q13 deletion, which was subsequently found in one other family. The 32 kb deleted region harbors the CYP2A7 gene and was enriched with enhancer, repressor and insulator sites. The wildtype allele was lost in the polyps of the proband. Further, real-time RT-PCR assays showed that expressions of MIA and MIA-RAB4B located 35 kb upstream of the deletion, were up-regulated in the polyps compared to the matched mucosa of the proband. MIARAB4B, the read-through long non-coding RNA (lncRNA), RAB4B, PIM2 and TAOK1 share common binding site of a microRNA, miR-24, in their 3'UTRs. PIM2 and TAOK1, two target oncogenes of miR-24, were co-ordinately up-regulated with MIA-RAB4B in the polyps, suggesting that MIA-RAB4B could function as competitive endogenous RNA to titrate miR-24 away from its other targets. The data suggest that the 19.13 deletion disrupted chromatin boundary, leading to altered expression of several genes and lncRNA, could contribute to colorectal cancer via novel genetic and epigenetic mechanisms. © 2017 Thean et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20191101 | |
dc.subject | long untranslated RNA | |
dc.subject | MIA protein | |
dc.subject | microRNA 24 | |
dc.subject | oncoprotein | |
dc.subject | PIM2 protein | |
dc.subject | RAB4B protein | |
dc.subject | TAOK1 protein | |
dc.subject | unclassified drug | |
dc.subject | CYP2A7 protein, human | |
dc.subject | cytochrome P450 family 2 | |
dc.subject | EGLN2 protein, human | |
dc.subject | hypoxia inducible factor proline dioxygenase | |
dc.subject | long untranslated RNA | |
dc.subject | MIA protein, human | |
dc.subject | scleroprotein | |
dc.subject | tumor protein | |
dc.subject | unspecific monooxygenase | |
dc.subject | 3' untranslated region | |
dc.subject | adenomatous polyposis coli gene | |
dc.subject | adult | |
dc.subject | Article | |
dc.subject | binding site | |
dc.subject | case report | |
dc.subject | chromosome 19q | |
dc.subject | chromosome 19q13 | |
dc.subject | colorectal cancer | |
dc.subject | controlled study | |
dc.subject | CYP2A7 gene | |
dc.subject | familial colon polyposis | |
dc.subject | gene | |
dc.subject | gene deletion | |
dc.subject | gene dosage | |
dc.subject | gene expression | |
dc.subject | gene location | |
dc.subject | gene mutation | |
dc.subject | gene targeting | |
dc.subject | genetic association | |
dc.subject | heterozygosity | |
dc.subject | human | |
dc.subject | male | |
dc.subject | real time polymerase chain reaction | |
dc.subject | reverse transcription polymerase chain reaction | |
dc.subject | upregulation | |
dc.subject | young adult | |
dc.subject | chromosome 19 | |
dc.subject | colon polyposis | |
dc.subject | colorectal tumor | |
dc.subject | female | |
dc.subject | genetics | |
dc.subject | pedigree | |
dc.subject | tumor suppressor gene | |
dc.subject | Adenomatous Polyposis Coli | |
dc.subject | Aryl Hydrocarbon Hydroxylases | |
dc.subject | Chromosomes, Human, Pair 19 | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Cytochrome P450 Family 2 | |
dc.subject | Extracellular Matrix Proteins | |
dc.subject | Female | |
dc.subject | Genes, APC | |
dc.subject | Humans | |
dc.subject | Hypoxia-Inducible Factor-Proline Dioxygenases | |
dc.subject | Male | |
dc.subject | Neoplasm Proteins | |
dc.subject | Pedigree | |
dc.subject | RNA, Long Noncoding | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1371/journal.pone.0173772 | |
dc.description.sourcetitle | PLoS ONE | |
dc.description.volume | 12 | |
dc.description.issue | 3 | |
dc.description.page | e0173772 | |
Appears in Collections: | Elements Staff Publications |
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