title: The RNA-binding protein HuR opposes the repression of ERBB-2 gene expression by microRNA miR-331-3p in prostate cancer cells.
abstract: ERBB-2 overexpression is associated with the development and progression of cancer and mediates its resistance to therapy. It has been suggested that post-transcriptional mechanisms control the overexpression of ERBB-2 in prostate cancer (PCa). We recently demonstrated that the 3'-untranslated region (3'-UTR) of ERBB-2 mRNA contains two specific target sites for binding of the microRNA miR-331-3p and that miR-331-3p represses ERBB-2 expression and signaling in PCa cells. Here we investigate a U-rich element situated in close proximity to the distal miR-331-3p target site in the ERBB-2 3'-UTR. Specific binding of HuR to this U-rich element promotes ERBB-2 expression in PCa cells. We show that HuR antagonizes the repressive action of miR-331-3p on its distal ERBB-2 3'-UTR target site. These results support a model in which the interplay between RNA-binding proteins and microRNAs controls the post-transcriptional regulation of gene expression and suggest that both HuR and miR-331-3p participate in the overexpression of ERBB-2 observed in some PCas.
authors.affiliation: Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Epis
authors.affiliation: Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barker
authors.affiliation: Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Giles
authors.affiliation: Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
authors.forename: Dianne J
authors.initials: DJ
authors.lastname: Beveridge
authors.affiliation: Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Royal Perth Hospital, Perth, Western Australia 6000, Australia; School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia 6008, Australia. Electronic address: peterl@waimr.uwa.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Leedman
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D045744:Cell Line, Tumor; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; D035683:MicroRNAs; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C544460:MIRN331 microRNA, human; C508053:ERBB2 protein, human