<scp>MicroRNA</scp>‐542‐3p inhibits tumour angiogenesis by targeting Angiopoietin‐2

Journal of Pathology - Tập 232 Số 5 - Trang 499-508 - 2014
Ting He1, Feifei Qi1, Lin Jia1, Shan Wang1, Nan Song1, Lifang Guo1, Yan Fu1, Yongzhang Luo1
1National Engineering Laboratory for Anti-tumour Protein Therapeutics, Beijing Key Laboratory for Protein Therapeutics and Cancer Biology Laboratory, and School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.

Tóm tắt

AbstractAngiopoietin‐2 (Angpt2) plays a critical role in angiogenesis and tumour progression. Therapeutic targeting of Angpt2 has been implicated as a promising strategy for cancer treatment. Whereas miRNAs are emerging as important modulators of angiogenesis, regulation of Angpt2 by miRNAs has not been established. Here we firstly report that Ang2 is targeted by a microRNA, miRNA‐542‐3p, which inhibits tumour progression by impairing Ang2's pro‐angiogenic activity. In cultured endothelial cells, miR‐542‐3p inhibited translation of Angpt2 mRNA by binding to its 3′ UTR, and addition of miR‐542‐3p to cultured endothelial cells attenuated angiogenesis. Administration of miR‐542‐3p to tumour‐bearing mice reduced tumour growth, angiogenesis and metastasis. Furthermore, the level of miR‐542‐3p in primary breast carcinomas correlated inversely with clinical progression in primary tumour samples from stage III and IV patients. Together, these findings uncover a novel regulatory pathway whereby an anti‐angiogenic miR‐542‐3p directly targets the key angiogenesis‐promoting protein Angpt2, suggesting that miR‐542‐3p may represent a promising target for anti‐angiogenic therapy and a potential marker for monitoring disease progression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

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Tài liệu tham khảo

10.1016/j.jpedsurg.2006.09.048

10.1038/nm.2537

10.1038/nrc1093

10.1126/science.277.5322.55

10.1038/nrc2894

10.1038/nrm2639

Saharinen P, 2010, How do angiopoietins Tie with vascular endothelial growth factors?, Curr Opin Hematol, 17, 198

10.1158/0008-5472.CAN-08-4382

10.1016/S1534-5807(02)00217-4

10.1158/1078-0432.CCR-10-0171

10.1016/j.ccr.2011.02.005

10.1016/j.ccr.2010.07.001

10.1093/jnci/djs009

10.1038/nrg2290

10.1126/scisignal.252pe1

10.1016/j.cell.2004.12.035

10.1101/gr.082701.108

10.1182/blood-2007-01-064428

10.1182/blood-2005-07-2961

10.1158/0008-5472.CAN-08-2007

10.1016/j.bbrc.2008.03.133

10.4049/jimmunol.0902378

10.1083/jcb.143.5.1341

10.1007/s00430-009-0111-z

10.1038/ng1536

10.1093/nar/gkm995

10.1016/j.bbrc.2003.08.086

10.1016/j.febslet.2010.08.025

10.1371/journal.pone.0029770

10.1158/0008-5472.CAN-10-4635

10.4049/jimmunol.178.11.7405

10.1016/j.celrep.2013.07.021

10.1111/j.1572-0241.2007.01377.x

10.3109/00365521.2012.746391

10.1378/chest.06-2915

10.1007/978-94-007-6627-3_46

Gu J, 2006, Hypoxia‐induced up‐regulation of angiopoietin‐2 in colorectal cancer, Oncol Rep, 15, 779

10.1158/1078-0432.CCR-08-1615

10.1046/j.1365-2362.2003.01243.x

10.1007/s12253-011-9387-6

10.1038/nrd3455

10.1016/S0161-6420(95)30875-5

10.1038/nm0195-27

Thông tin
Thông tin xuất bản

Journal of Pathology

Tập 232 Số 5

499-508

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