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Loss of Repression of HuR Translation by miR‐16 May Be Responsible for the Elevation of HuR in Human Breast Carcinoma
Author(s) -
Xu Fang,
Zhang Xiaotian,
Lei Yutao,
Liu Xinwen,
Liu Zhenyun,
Tong Tanjun,
Wang Wengong
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22762
Subject(s) - gene knockdown , microrna , messenger rna , three prime untranslated region , untranslated region , translation (biology) , translational regulation , psychological repression , au rich element , cancer research , breast carcinoma , luciferase , rna binding protein , microbiology and biotechnology , biology , breast cancer , gene expression , cancer , transfection , apoptosis , cell culture , gene , genetics
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. J. Cell. Biochem. 111: 727–734, 2010. © 2010 Wiley‐Liss, Inc.