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AuthorIbrahim-Alobaide, Mohammed A.
AuthorAbdelsalam, Abdelsalam G.
AuthorAlobydi, Hytham
AuthorRasul, Kakil Ibrahim
AuthorZhang, Ruiwen
AuthorSrivenugopal, Kalkunte S.
Available date2016-11-17T08:56:19Z
Publication Date2014-11-27
Publication NameMolecular and Clinical Oncology
Identifierhttp://dx.doi.org/10.3892/mco.2014.468
CitationIBRAHIM-ALOBAIDE MA, ABDELSALAM AG, ALOBYDI H, RASUL KI, ZHANG R, SRIVENUGOPAL KS. Characterization of regulatory sequences in alternative promoters of hypermethylated genes associated with tumor resistance to cisplatin. Molecular and Clinical Oncology. 2015;3(2):408-414
ISSN2049-9450
URIhttp://hdl.handle.net/10576/5020
AbstractThe development of cisplatin resistance in human cancers is controlled by multiple genes and leads to therapeutic failure. Hypermethylation of specific gene promoters is a key event in clinical resistance to cisplatin. Although the usage of multiple promoters is frequent in the transcription of human genes, the role of alternative promoters and their regulatory sequences have not yet been investigated in cisplatin resistance genes. In a new approach, we hypothesized that human cancers exploit the specific transcription factor-binding sites (TFBS) and CpG islands (CGIs) located in the alternative promoters of certain genes to acquire platinum drug resistance. To provide a useful resource of regulatory elements associated with cisplatin resistance, we investigated the TFBS and CGIs in 48 alternative promoters of 14 hypermethylated cisplatin resistance genes previously reported. CGIs prone to methylation were identified in 28 alternative promoters of 11 hypermethylated genes. The majority of alternative promoters harboring CGIs (93%) were clustered in one phylogenetic subclass, whereas the ones lacking CGIs were distributed in two unrelated subclasses. Regulatory sequences, initiator and TATA-532 prevailed over TATA-8 and were found in all the promoters. B recognition element (BRE) sequences were present only in alternative promoters harboring CGIs, but CCAAT and TAACC were found in both types of alternative promoters, whereas downstream promoter element sequences were significantly less frequent. Therefore, it was hypothesized that BRE and CGI sequences co-localized in alternative promoters of cisplatin resistance genes may be used to design molecular markers for drug resistance. A more extensive knowledge of alternative promoters and their regulatory elements in clinical resistance to cisplatin is likely to usher novel avenues for sensitizing human cancers to treatment.
SponsorCancer Prevention and Research Institute of Texas (CPRIT; no. RP130266)
Languageen
PublisherSpandidos Publications
Subjectalternative promoters
cisplatin resistance
CpG islands
DNA methylation
transcription factor-binding sites
bioinformatics
TitleCharacterization of regulatory sequences in alternative promoters of hypermethylated genes associated with tumor resistance to cisplatin
TypeArticle
Pagination408-414
Issue Number2
Volume Number3
dc.accessType Open Access


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