title: Understanding the transcriptional regulation of cervix cancer using microarray gene expression data and promoter sequence analysis of a curated gene set.
abstract: Cervical cancer, the malignant neoplasm of the cervix uteri is the second most common cancer among women worldwide and the top-most cancer in India. Several factors are responsible for causing cervical cancer, which alter the expression of oncogenic genes resulting in up or down-regulation of gene expression and inactivation of tumor-suppressor genes/gene products. Gene expression is regulated by interactions between transcription factors (TFs) and specific regulatory elements in the promoter regions of target genes. Thus, it is important to decipher and analyze TFs that bind to regulatory regions of diseased genes and regulate their expression. In the present study, computational methods involving the combination of gene expression data from microarray experiments and promoter sequence analysis of a curated gene set involved in the cervical cancer causation have been utilized for identifying potential regulatory elements. Consensus predictions of two approaches led to the identification of twelve TFs that might be crucial to the regulation of cervical cancer progression. Subsequently, TF enrichment and oncomine expression analysis suggested that the transcription factor family E2F played an important role for the regulation of genes involve in cervical carcinogenesis. Our results suggest that E2F possesses diagnostic/prognostic value and can act as a potential drug target in cervical cancer.
authors.affiliation: Integrative Genomics and Medicine, MRC Clinical Sciences, Imperial College, London, UK.
authors.forename: Prashant
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: Bioinformatics Division, Institute of Cytology and Preventive Oncology, Noida-201301, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Mangal
authors.affiliation: Bioinformatics Division, Institute of Cytology and Preventive Oncology, Noida-201301, India. Electronic address: smagarwal@yahoo.com.
authors.forename: Subhash Mohan
authors.initials: SM
authors.lastname: Agarwal
mesh_terms: D001665:Binding Sites; D016000:Cluster Analysis; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014157:Transcription Factors
keywords: CCDB; CIP2A; Cervical cancer; E2F; HPV; MARA; Microarray; TFBS; TFs; TSS; Transcription factors; cancerous inhibitor of protein phosphatase 2A; cervical cancer gene database; human papillomavirus; motif activity response analysis; transcription factor binding site; transcription factors; transcription start site