Investigating the role of RNA-binding proteins (RBPS) in explaining differential gene expression in cancer

Download
2016
Lafzi, Atefeh
Most of the studies on cancer have tried to explain the observed differential gene expression considering only transcriptional regulation. However, post-transcriptional regulation (PTR) has been increasingly recognized as a complex mechanism that also controls various steps of gene expression regulation. Post-transcritional regulation is governed by the interactions of RNA-binding proteins (RBPs) and microRNAs (miRNAs) with their target genes. In this thesis, having found that several RBPs are differentially expressed in Lung squamous cell carcinoma (LUSC), we developed a statistical model which incorporates copy number variation, DNA Methylation and the regulatory effects of transcription factors, miRNAs and RBPs to predict gene expression in cancer. Including RBP-based regulation in addition to other features significantly increased the Spearman rank correlation between predicted and measured expression of held-out genes. Using a feature selection procedure we identified the candidate RBP regulators in LUSC and confirmed that many of them are also differentially expressed. We also determined the targets of these RBPs and compared them with CLIP-determined targets. Lastly, we performed Kaplan-Meier survival analysis, and showed that some of our candidate RBP regulators have prognostic power in LUSC. Our results suggest that the regulatory effects of RBPs have to be considered to explain differential gene expression in cancer.

Suggestions

Mathematical Modeling and Approximation of Gene Expression Patterns
Yılmaz, Fatih; Öktem, Hüseyin Avni (2004-09-03)
This study concerns modeling, approximation and inference of gene regulatory dynamics on the basis of gene expression patterns. The dynamical behavior of gene expressions is represented by a system of ordinary differential equations. We introduce a gene-interaction matrix with some nonlinear entries, in particular, quadratic polynomials of the expression levels to keep the system solvable. The model parameters are determined by using optimization. Then, we provide the time-discrete approximation of our time...
DETERMINATION OF THE RELATIONSHIP BETWEEN DOXORUBICIN RESISTANCE AND WNT SIGNALING PATHWAY IN HELA AND K562 CELL LINES
Mutlu, Pelin; Pourianazar, Negar Taghavi; Yucel, Meral; Gündüz, Ufuk (2018-01-01)
Activation of the Wnt signaling in some types of cancer and its relation with chemotherapy resistance is a very interesting issue that has been emphasized in recent years. Although, it is known that increase in the activity of beta-catenin is important in blast transformation and drug resistance, the underlying mechanisms are still unclear. In this study, changes in the expression levels of 186 genes that are thought to be important in drug resistance and Wnt signaling pathways were determined by using qPCR...
Prediction of protein subcellular localization using global protein sequence feature
Bozkurt, Burçin; Atalay, Mehmet Volkan; Department of Computer Engineering (2003)
The problem of identifying genes in eukaryotic genomic sequences by computational methods has attracted considerable research attention in recent years. Many early approaches to the problem focused on prediction of individual functional elements and compositional properties of coding and non coding deoxyribonucleic acid (DNA) in entire eukaryotic gene structures. More recently, a number of approaches has been developed which integrate multiple types of information including structure, function and genetic p...
Sequence specific inhibition of human chemokine gene, cxcl7, by small interfering RNAS in lewis lung carcinoma cells
Kızışar, Dilay; Akkaya, Mahinur S.; Department of Chemistry (2013)
In this study, we aimed to design small interfering RNAs to silence the expression of a gene that is a member of chemokines playing crucial roles on cancer. Small interfering RNAs (siRNAs) are generated by ribonuclease III cleavage of 20-25nt in length dsRNAs which mediate RNAi-induced specific mRNA degradation and they are known to be an important part of the gene regulation mechanism in all Eukaryotes. Recently, siRNAs are being utilized as promising treatment approaches. In this study, we targeted a gene...
Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group
Mutlu, M.; Mutlu, Pelin; Azarkan, S.; Baylr, Ö.; Öcal, B.; Saylam, G.; KORKMAZ, MEHMET HAKAN (2021-03-23)
Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dlşkapl Y...
Citation Formats
A. Lafzi, “Investigating the role of RNA-binding proteins (RBPS) in explaining differential gene expression in cancer,” M.S. - Master of Science, Middle East Technical University, 2016.