An Investigation of HNRNPA1 functions in breast cancer

Download

index.pdf

Date

2019

Author

Özgül, İbrahim

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

286
views

122
downloads

Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is an RNA-binding protein with a broad range of functions including transcriptional and translational regulation of mRNAs, transport of mRNAs from the nucleus, alternative splicing, telomere maintenance, and miRNA processing. Among all, miRNA related functions of HNRNPA1 are the least understood. Hence, in this study, we aim to investigate potential miRNAs regulated by HNRNPA1.Using HNRNPA1-silenced MCF7 cells, we identified several notable miRNAs using NanoString technology that responded to the loss of HNRNPA1. One of these miRNAs was mir-21, an oncogenic miRNA, that is significantly downregulated in response to loss of HNRNPA1. Furthermore, CRISPR/Cas9 deletion of HNRNPA1 showed downregulated pri-mir-21 levels with little to no change in the host gene (VMP1) expression. Three different mRNA targets of mir-21(STAT3, BCL2, and PDCD4) also showed upregulation upon HNRNPA1 deletion. Mir-21 is a well-accepted oncogenic miRNA that has potential diagnostic and therapeutic roles in many different cancers. Therefore, understanding the regulatory mechanisms behind mir-21 levels in cancer is of interest. Results suggest that HNRNPA1 may regulate the mir-21 levels in breast cancer cell line MCF7. Future studies will provide a more detailed mechanistic explanation.

Subject Keywords

MicroRNA., HNRNPA1, miRNA, Breast Cancer.

URI

http://etd.lib.metu.edu.tr/upload/12623783/index.pdf
https://hdl.handle.net/11511/44092

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

An Investigation of poly(A) site selection loci in estrogen treated breast cancer cells Bekar, Damla; Erson Bensan, A. Elif.; Department of Biology (2019) 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 ho...
Stochastic modelling of the MAPK signalling pathway Purutçuoğlu Gazi, Vilda (null; 2006-06-01) The MAPK (mitogen-activated protein kinase) or its synonymous ERK (extracellular signal regulated kinase) pathway whose components are Ras, Raf, and MEK proteins with many biochemical links, is one of the major signalling systems involved in cellular growth control of eukaryotes including cell proliferation, transformation, differentiation, and apoptosis. Because of its diverse functionality, it is also activated in a variety of hormone activation and many illnesses, which have multi-complex gene structure ...
Analysis of motifs in microRNA-transcription factor gene regulatory networks Sürün, Bilge; Acar, Aybar Can; Purutçuoğlu Gazi, Vilda; Department of Bioinformatics (2014) MicroRNAs are small non-coding RNA molecules which contain 21-25 nucleotides, and function in post transcriptional regulation by inhibiting the translation of mRNA targets. miRNAs typically affect gene regulation by forming composite feed forward circuits (cFFCs) which also comprise a transcription factor (TF) and a target gene. By analyzing these cFFCs, the contribution of miRNAs in altering TF networks can be revealed. These contributions could either be the de-escalation of the target gene repertoire or ...
Molecular docking study of fda-approved drugs to inhibit the bacterial ribosome Ateş, Beril; Yüce, Merve; Levitaş, Ozge Kurkcuoglu; Sungur, Fethiye Aylin (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10) Ribosomes are large macromolecular complexes responsible for cellular protein synthesis. It consists of two subunits; called 30S small and 50S large subunits in bacteria, involving antibiotic binding regions. This mac- romolecular machine is one of the significant targets of conventional antibiotics because protein synthesis can be stopped by targeting functional sites in the ribosome. For instance, several antibiotics target the decoding center responsible for deciphering the genetic code, as well as mRNA ...
MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system Erson Bensan, Ayşe Elif (2008-10-01) Since the discovery of microRNAs (miRNAs) in Caenorhabditis elegans, mounting evidence illustrates the important regulatory roles for miRNAs in various developmental, differentiation, cell proliferation, and apoptosis pathways of diverse organisms. We are just beginning to elucidate novel aspects of RNA mediated gene regulation and to understand how heavily various molecular pathways rely on miRNAs for their normal function. miRNAs are small non-protein-coding transcripts that regulate gene expression post-...

Citation Formats

İ. Özgül, “An Investigation of HNRNPA1 functions in breast cancer,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Molecular Biology and Genetics, Middle East Technical University, 2019.