Loss of repression of HuR translation by miR-16 may be responsible for the elevation of HuR in human breast carcinoma.
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.
Xu
Fang
F
Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.
Zhang
Xiaotian
X
Lei
Yutao
Y
Liu
Xinwen
X
Liu
Zhenyun
Z
Tong
Tanjun
T
Wang
Wengong
W
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
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