An Investigation of poly(A) site selection loci in estrogen treated breast cancer cells

Bekar, Damla
Alternative polyadenylation (APA) is an mRNA processing step implicated in 3’UTR (Untranslated Region) isoform diversity, which may have significant impacts on protein levels. Nearly 70% of known human genes harbor multiple polyA sites. Proliferative signals, developmental cues and tissue specificity can induce alternative selection of polyA sites, producing transcripts with different 3’UTR lengths. Given that APA generates a vast isoform diversity, there are possible mechanistic explanations emerging on how APA might be regulated. To better understand the APA mechanism in the presence of proliferative signals, we chose a model system where we know APA is induced by Estradiol (E2) in Estrogen positive (ER+) breast cancer cell line. We analyzed existing Chromatin Immunoprecipitation- Sequencing (ChIP- Seq) data for certain histone marks that may overlap with polyA sites in E2 treated cells and performed experiments to confirm usage of these specific polyA sites. Despite the low number of cases we could analyze in this study, our results may suggest a possible link between E2 regulated transcription and APA. Future high throughput experiments will be important to test how widespread these correlations are and what the underlying mechanisms are.


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MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. Some miRNAs act as tumor suppressors and are downregulated in cancers such as miR-125b in breast cancer cell lines and tumors. Earlier, we developed a miR-125b expression model system and performed a transcriptomics experiment. Among many indirect targets, ALCAM (activated leukocyte antigen molecule) appeared to be very significantly upregulated in MCF7-125b cell...
Citation Formats
D. Bekar, “An Investigation of poly(A) site selection loci in estrogen treated breast cancer cells,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Biology., Middle East Technical University, 2019.