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An Investigation of HNRNPA1 functions in breast cancer

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2019
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.