A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer

被引：108

作者：

Wu, Sherry Y. ^{[1
]}

Rupaimoole, Rajesha ^{[1
]}

Shen, Fangrong ^{[1
,2
]}

Pradeep, Sunila ^{[1
]}

Pecot, Chad V. ^{[3
,4
]}

Ivan, Cristina ^{[1
,5
]}

Nagaraja, Archana S. ^{[1
]}

Gharpure, Kshipra M. ^{[1
]}

Pham, Elizabeth ^{[1
,6
]}

Hatakeyama, Hiroto ^{[1
]}

McGuire, Michael H. ^{[1
]}

Haemmerle, Monika ^{[1
]}

Vidal-Anaya, Viviana ^{[1
]}

Olsen, Courtney ^{[1
]}

Rodriguez-Aguayo, Cristian ^{[3
,7
]}

Filant, Justyna ^{[1
]}

Ehsanipour, Ehsan A. ^{[8
]}

Herbrich, Shelley M. ^{[1
,9
]}

Maiti, Sourindra N. ^{[10
]}

Huang, Li ^{[8
]}

Kim, Ji Hoon ^{[11
]}

Zhang, Xinna ^{[5
]}

Han, Hee-Dong ^{[1
,12
]}

Armaiz-Pena, Guillermo N. ^{[1
]}

Seviour, Elena G. ^{[11
]}

Tucker, Sue ^{[9
]}

Zhang, Min ^{[13
]}

Yang, Da ^{[13
]}

Cooper, Laurence J. N. ^{[10
]}

Ali-Fehmi, Rouba ^{[14
]}

Bar-Eli, Menashe ^{[8
]}

Lee, Ju-Seog ^{[11
]}

Ram, Prahlad T. ^{[11
]}

Baggerly, Keith A. ^{[9
]}

Lopez-Berestein, Gabriel ^{[4
,7
]}

Hung, Mien-Chie ^{[15
,16
]}

Sood, Anil K. ^{[1
,5
,8
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA

[2] Soochow Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Suzhou 215006, Jiangsu, Peoples R China

[3] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA

[4] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA

[5] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA

[6] Sunnybrook Res Inst, Biol Sci Platform, Toronto, ON M4N 3M5, Canada

[7] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[12] Konkuk Univ, Sch Med, Dept Immunol Lab, Chungju 380701, South Korea

[13] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA

[14] Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA

[15] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[16] China Med Univ, Ctr Mol Med, Taichung 40402, Taiwan

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

加拿大健康研究院;

关键词：

EARLY GROWTH RESPONSE-1; EPITHELIAL-MESENCHYMAL TRANSITION; CELL-PROLIFERATION; OVARIAN-CANCER; TUMOR ANGIOGENESIS; COLORECTAL-CANCER; PROGNOSTIC VALUE; MICRORNAS; 192; IN-VITRO; EXPRESSION;

D O I：

10.1038/ncomms11169

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A deeper mechanistic understanding of tumour angiogenesis regulation is needed to improve current anti-angiogenic therapies. Here we present evidence from systems-based miRNA analyses of large-scale patient data sets along with in vitro and in vivo experiments that miR-192 is a key regulator of angiogenesis. The potent anti-angiogenic effect of miR-192 stems from its ability to globally downregulate angiogenic pathways in cancer cells through regulation of EGR1 and HOXB9. Low miR-192 expression in human tumours is predictive of poor clinical outcome in several cancer types. Using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes, we show that miR-192 delivery leads to inhibition of tumour angiogenesis in multiple ovarian and renal tumour models, resulting in tumour regression and growth inhibition. This anti-angiogenic and anti-tumour effect is more robust than that observed with an anti-VEGF antibody. Collectively, these data identify miR-192 as a central node in tumour angiogenesis and support the use of miR-192 in an anti-angiogenesis therapy.

引用

页数：14

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