title: Loss of repression of HuR translation by miR-16 may be responsible for the elevation of HuR in human breast carcinoma.
abstract: Elevated levels of RNA binding protein HuR were found in various human cancers. However, the mechanisms underlying HuR over-expression in cancers have not been fully elucidated. Here, we show that miR-16 acts as a novel post-transcriptional regulator for HuR. Knockdown of miR-16 increased HuR protein levels in MDA-MB-231 cells, while over-expression of pre-miR16 reduced HuR expression. Neither knockdown nor over-expression of miR-16 could alter the mRNA levels of HuR. Instead, knockdown of miR-16 increased the level of de novo synthesized HuR protein. Importantly, mechanistic studies showed that miR-16 associated with the 3'UTR of HuR, and knockdown of miR-16 markedly increased the luciferase activity of a HuR 3'UTR-containing reporter. We further demonstrate that the level of miR-16 was inversely correlated with HuR protein level in human breast carcinoma. Together, our results suggest an important role of miR-16 in regulating HuR translation and link this regulatory pathway to human breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhang
authors.forename: Yutao
authors.initials: Y
authors.lastname: Lei
authors.forename: Xinwen
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenyun
authors.initials: Z
authors.lastname: Liu
authors.forename: Tanjun
authors.initials: T
authors.lastname: Tong
authors.forename: Wengong
authors.initials: W
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins