Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs

被引：1188

作者：

Tay, Yvonne ^{[1
]}

Kats, Lev ^{[1
]}

Salmena, Leonardo ^{[1
]}

Weiss, Dror ^{[1
]}

Tan, Shen Mynn ^{[2
,3
,4
]}

Ala, Ugo ^{[1
,5
,6
]}

Karreth, Florian ^{[1
]}

Poliseno, Laura ^{[1
]}

Provero, Paolo ^{[5
,6
]}

Di Cunto, Ferdinando ^{[5
,6
]}

Lieberman, Judy ^{[2
,3
,4
]}

Rigoutsos, Isidore ^{[7
]}

Pandolfi, Pier Paolo ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Canc Genet Program,Beth Israel Deaconess Med Ctr, Div Genet,Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[5] Univ Turin, Mol Biotechnol Ctr, Turin, Italy

[6] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy

[7] Thomas Jefferson Univ, Computat Med Ctr, Jefferson Med Coll, Philadelphia, PA 19107 USA

来源：

CELL | 2011年 / 147卷 / 02期

基金：

加拿大健康研究院;

关键词：

MICRORNA; IDENTIFICATION; EXPRESSION; GENE; REGIONS; TARGETS; PROTEIN; CLUSTER;

D O I：

10.1016/j.cell.2011.09.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Here, we demonstrate that protein-coding RNA transcripts can crosstalk by competing for common microRNAs, with microRNA response elements as the foundation of this interaction. We have termed such RNA transcripts as competing endogenous RNAs (ceRNAs). We tested this hypothesis in the context of PTEN, a key tumor suppressor whose abundance determines critical outcomes in tumorigenesis. By a combined computational and experimental approach, we identified and validated endogenous protein-coding transcripts that regulate PTEN, antagonize PI3K/AKT signaling, and possess growth-and tumor-suppressive properties. Notably, we also show that these genes display concordant expression patterns with PTEN and copy number loss in cancers. Our study presents a road map for the prediction and validation of ceRNA activity and networks and thus imparts a trans-regulatory function to protein-coding mRNAs.

引用

页码：344 / 357

页数：14

共 38 条

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Subtle variations in Pten dose determine cancer susceptibility [J].