AN ONCOGENIC ISOFORM SWITCH LEADS TO HNRNPA1 OVEREXPRESSION IN TRIPLE NEGATIVE BREAST CANCER

Download

10482266.pdf

Date

2022-8-05

Author

Erdem, Murat

Metadata

Show full item record

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

Item Usage Stats

191
views

97
downloads

HNRNPA1 is one of the most abundant and ubiquitously expressed nuclear proteins and plays a significant role in RNA biology. It has many diverse functions in cellular nucleic acid metabolisms, including mRNA transport, miRNA maturation, and telomere maintenance. Emerging evidence suggest HNRNPA1 to be an important RNA binding protein (RBP) to regulate various RNA related processes in cancer cells. However, deregulation of HNRNPA1 expression and its action mechanisms are unclear in breast cancers. The study aims to investigate the isoform level expression of HNRNPA1 and the role of HNRNPA1 in breast cancer models. Using expression data in GTEx and TCGA databases, and microarray data set, an isoform switch between the 3'UTR isoforms of HNRNPA1 was discovered in breast cancers. It is shown that the mammary tissue has a dominantly expressed isoform with a short half-life. On the other hand, this isoform is downregulated in breast cancers, favoring a much more stable isoform. It is shown that the overexpression of this stable isoform leads to increased HNRNPA1 protein levels. In turn, high HNRNPA1 protein levels correlate with poor survival in patients. In support of this, silencing of HNRNPA1 causes a reversal in neoplastic phenotypes, including proliferation, clonogenic potential, migration, and invasion. In addition, silencing of HNRNPA1 results in the downregulation of microRNAs that map to intragenic regions. Among the downregulated miRNAs, pri-miR-27b and its host gene (C9ORF3) expression were decreased, suggesting that pri-miR-27b and C9ORF3 expressions were co-regulated by HNRNPA1 at the transcriptional level in MDA-MB-231 cells. In summary, a cancer-specific isoform switch was identified for HNRNPA1 and a novel insight was provided on the function of HNRNPA1 in breast cancers.

Subject Keywords

APA, HNRNPA1, Isoform Switch, miR-27b, Breast Cancer

URI

https://hdl.handle.net/11511/98544

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Monitoring of Tryptophan as a Biomarker for Cancerous Cells in Terahertz (THz) Sensing Altan, Hakan; Gok, Seher; Ozyurt, Ipek; Severcan, Feride (2016-02-17) Tryptophan is an extremely important amino acid for a variety of biological functions in living organisms. Changes in the concentration of this amino acid can point to identification of cancerous tissues or even confirm symptoms of depression in patients. Therefore it is extremely important to identify and quantify tryptophan concentrations in human blood as well as in in-vivo diagnostic studies. Here a reflection based terahertz pulsed spectroscopy system was used to study the interaction of THz pulses wit...
APOBEC3B expression in drug resistant MCF-7 breast cancer cell lines Onguru, Onder; Yalcin, Serap; Rosemblit, Cinthia; Zhang, Paul J.; Kilic, Selim; Gündüz, Ufuk (2016-04-01) APOBEC3B belongs to a protein family of cytidine deaminases that can insert mutations in DNA and RNA as a result of their ability to deaminate cytidine to uridine. It has been shown that APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers. We investigated APOBEC3B expression in four drug resistant breast cancer cell lines (Doxorubicin, Etoposide, Paclitaxel and Docetaxel resistant MCF-7 cell lines) using a novel RNA in situ hybridization technology (RNAscope) and compare...
An Investigation of HNRNPA1 functions in breast cancer Özgül, İbrahim; Erson Bensan, Ayşe Elif; Department of Molecular Biology and Genetics (2019) 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 N...
IDENTIFYING ISOFORM SWITCHES IN BREAST CANCER HENDEN, Şevki Onur; Can, Tolga; Department of Computer Engineering (2021-9-9) Characterizing the human genome's molecular functions and their variations across people is vital for understanding the cellular processes behind human genetic characteristics and diseases. With the advent of single-cell RNA sequencing (scRNA-seq), it is now possible to investigate gene expression in individual cells. Although a number of scRNA-seq bioinformatics tools are now available, many of them focus on overall gene expression levels and, as a result, often ignore heterogeneity caused by individual tr...
The Q41R mutation in the HCV-protease enhances the reactivity towards MAVS by suppressing non-reactive pathways Zheng, Chen; Schneider, Markus; Marıon, Antoıne; Antes, Iris (2022-01-01) Recent experimental findings pointed out a new mutation in the HCV protease, Q41R, responsible for a significant enhancement of the enzyme's reactivity towards the mitochondrial antiviral-signaling protein (MAVS). The Q41R mutation is located rather far from the active site, and its involvement in the overall reaction mechanism is thus unclear. We used classical molecular dynamics and QM/MM to study the acylation reaction of HCV NS3/4A protease variants bound to MAVS and the NS4A/4B substrate and uncovered ...

Citation Formats

M. Erdem, “AN ONCOGENIC ISOFORM SWITCH LEADS TO HNRNPA1 OVEREXPRESSION IN TRIPLE NEGATIVE BREAST CANCER,” Ph.D. - Doctoral Program, Middle East Technical University, 2022.