An Investigation of HNRNPA1 functions in breast cancer

Özgül, İbrahim
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.


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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...
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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.