title: MicroRNA-16 modulates HuR regulation of cyclin E1 in breast cancer cells.
abstract: RNA binding protein (RBPs) and microRNAs (miRNAs or miRs) are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR) containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC). Despite this, miR-16 and HuR do not affect the other's expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. xunguo1128@gmail.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. mconnick@unm.edu.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Connick
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. jennmv1@icloud.com.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vanderhoof
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. mishak@salud.unm.edu.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Ishak
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. rhartley@salud.unm.edu.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Hartley
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000737:chemistry / Q000235:genetics*; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C475820:CCNE1 protein, human; D019927:Cyclin E; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D015513:Oncogene Proteins
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