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

共 57 条

[1] Early Growth Response-1 Regulates Angiopoietin-1-Induced Endothelial Cell Proliferation, Migration, and Differentiation [J].

Abdel-Malak, Nelly A. ;

Mofarrahi, Mahroo ;

Mayaki, Dominique ;

Khachigian, Levon M. ;

Hussain, Sabah N. A. .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2009, 29 (02) :209-216

[2] Expression of platelet-derived growth factor and activated receptor in clinical specimens of epithelial ovarian cancer and ovarian carcinoma cell lines [J].

Apte, SM ;

Bucana, CD ;

Killion, JJ ;

Gershenson, DM ;

Fidler, IJ .

GYNECOLOGIC ONCOLOGY, 2004, 93 (01) :78-86

[3] Src activation by β-adrenoreceptors is a key switch for tumour metastasis [J].

Armaiz-Pena, Guillermo N. ;

Allen, Julie K. ;

Cruz, Anthony ;

Stone, Rebecca L. ;

Nick, Alpa M. ;

Lin, Yvonne G. ;

Han, Liz Y. ;

Mangala, Lingegowda S. ;

Villares, Gabriel J. ;

Vivas-Mejia, Pablo ;

Rodriguez-Aguayo, Cristian ;

Nagaraja, Archana S. ;

Gharpure, Kshipra M. ;

Wu, Zheng ;

English, Robert D. ;

Soman, Kizhake V. ;

Shazhad, Mian M. K. ;

Zigler, Maya ;

Deavers, Michael T. ;

Zien, Alexander ;

Soldatos, Theodoros G. ;

Jackson, David B. ;

Wiktorowicz, John E. ;

Torres-Lugo, Madeline ;

Young, Tom ;

De Geest, Koen ;

Gallick, Gary E. ;

Bar-Eli, Menashe ;

Lopez-Berestein, Gabriel ;

Cole, Steve W. ;

Lopez, Gustavo E. ;

Lutgendorf, Susan K. ;

Sood, Anil K. .

NATURE COMMUNICATIONS, 2013, 4

[4] AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients [J].

Batchelor, Tracy T. ;

Sorensen, A. Gregory ;

di Tomaso, Emmanuelle ;

Zhang, Wei-Ting ;

Duda, Dan G. ;

Cohen, Kenneth S. ;

Kozak, Kevin R. ;

Cahill, Daniel P. ;

Chen, Poe-Jou ;

Zhu, Mingwang ;

Ancukiewicz, Marek ;

Mrugala, Maciej M. ;

Plotkin, Scott ;

Drappatz, Jan ;

Louis, David N. ;

Ivy, Percy ;

Scadden, David T. ;

Benner, Thomas ;

Loeffler, Jay S. ;

Wen, Patrick Y. ;

Jain, Rakesh K. .

CANCER CELL, 2007, 11 (01) :83-95

[5] Resistance and Escape From Antiangiogenesis Therapy: Clinical Implications and Future Strategies [J].

Bottsford-Miller, Justin N. ;

Coleman, Robert L. ;

Sood, Anil K. .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (32) :4026-4034

[6] p53-Responsive MicroRNAs 192 and 215 Are Capable of Inducing Cell Cycle Arrest [J].

Braun, Christian J. ;

Zhang, Xin ;

Savelyeva, Irina ;

Wolff, Sonja ;

Moll, Ute M. ;

Schepeler, Troels ;

Orntoft, Torben F. ;

Andersen, Claus L. ;

Dobbelstein, Matthias .

CANCER RESEARCH, 2008, 68 (24) :10094-10104

[7] Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer [J].

Burger, Robert A. ;

Brady, Mark F. ;

Bookman, Michael A. ;

Fleming, Gini F. ;

Monk, Bradley J. ;

Huang, Helen ;

Mannel, Robert S. ;

Homesley, Howard D. ;

Fowler, Jeffrey ;

Greer, Benjamin E. ;

Boente, Matthew ;

Birrer, Michael J. ;

Liang, Sharon X. .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (26) :2473-2483

[8] Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors [J].

Casanovas, O ;

Hicklin, DJ ;

Bergers, G ;

Hanahan, D .

CANCER CELL, 2005, 8 (04) :299-309

[9] microRNA-192,-194 and-215 are frequently downregulated in colorectal cancer [J].

Chiang, Yeunpo ;

Song, Yongxi ;

Wang, Zhenning ;

Liu, Zhuangkai ;

Gao, Peng ;

Liang, Jiwang ;

Zhu, Jinliang ;

Xing, Chengzhong ;

Xu, Huimian .

EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2012, 3 (03) :560-566

[10] miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes [J].

Dweep, Harsh ;

Sticht, Carsten ;

Pandey, Priyanka ;

Gretz, Norbert .

JOURNAL OF BIOMEDICAL INFORMATICS, 2011, 44 (05) :839-847

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