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

Sherry Y. Wu; Rajesha Rupaimoole; Fangrong Shen; Sunila Pradeep; Chad V. Pecot; Cristina Ivan; Archana S. Nagaraja; Kshipra M. Gharpure; Elizabeth Pham; Hiroto Hatakeyama; Michael H. McGuire; Monika Haemmerle; Viviana Vidal-Anaya; Courtney Olsen; Cristian Rodriguez-Aguayo; Justyna Filant; Ehsan A. Ehsanipour; Shelley M. Herbrich; Sourindra N. Maiti; Li Huang; Ji Hoon Kim; Xinna Zhang; Hee Dong Han; Guillermo N. Armaiz-Pena; Elena G. Seviour; Sue Tucker; Min Zhang; Da Yang; Laurence J.N. Cooper; Rouba Ali-Fehmi; Menashe Bar-Eli; Ju Seog Lee; Prahlad T. Ram; Keith A. Baggerly; Gabriel Lopez-Berestein; Mien Chie Hung; Anil K. Sood

doi:10.1038/ncomms11169

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

Sherry Y. Wu, Rajesha Rupaimoole, Fangrong Shen, Sunila Pradeep, Chad V. Pecot, Cristina Ivan, Archana S. Nagaraja, Kshipra M. Gharpure, Elizabeth Pham, Hiroto Hatakeyama, Michael H. McGuire, Monika Haemmerle, Viviana Vidal-Anaya, Courtney Olsen, Cristian Rodriguez-Aguayo, Justyna Filant, Ehsan A. Ehsanipour, Shelley M. Herbrich, Sourindra N. Maiti, Li HuangJi Hoon Kim, Xinna Zhang, Hee Dong Han, Guillermo N. Armaiz-Pena, Elena G. Seviour, Sue Tucker, Min Zhang, Da Yang, Laurence J.N. Cooper, Rouba Ali-Fehmi, Menashe Bar-Eli, Ju Seog Lee, Prahlad T. Ram, Keith A. Baggerly, Gabriel Lopez-Berestein, Mien Chie Hung, Anil K. Sood

Research output: Contribution to journal › Article › peer-review

106 Citations (Scopus)

Abstract

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.

Original language	English
Article number	11169
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11169
Publication status	Published - 2016 Apr 4
Externally published	Yes

Bibliographical note

Funding Information:
S.Y.W. is supported by the Ovarian Cancer Research Fund Alliance, Foundation for Womens Cancer, Texas Center for Cancer Nanomedicine and the Cancer Prevention Research Institute of Texas training grants (RP101502 and RP101489). R.R. is supported by the Russell and Diana Hawkins Family Foundation Discovery Fellowship. F.S. is supported by the Jiangsu Health International Exchange Program Fellowship. S.P. and G.N.A.-P. are supported by the Foundation for Womens Cancer. C.V.P. was supported by the NCI T32 training grant CA009666. E.P. is supported by a postdoctoral fellowship from the Canadian Institutes of Health Research and a Trainee Travel Award from Ovarian Cancer Canada. M.H. is supported by the Deutsche Forschungsgemeinschaft Research Fellowship. L.J.N.C. has ownership interests at Intrexon, Targazyme and Ziopharm; has patents with Sangamo BioSciences, reports receiving speakers bureau honoraria from Miltenyi; is a consultant/advisory board member for Ferring Pharmaceuticals and GE Healthcare; and reports receiving commercial research grants from Immatics US. Portions of this work were supported by the NIH (GM100777-01, GM086937-01, GM084552-04, CA016672, CA109298, P50 CA083639, P50 CA098258, CA128797, U54 CA151668, UH2 TR000943, U24CA143835 and P30CA16672), NCI-DHHS-NIH T32 Training grant (T32 CA101642), the DOD (OC120547 and OC093416), the Ovarian Cancer Research Fund, Inc. (Program Project Development Grant), the Blanton-Davis Ovarian Cancer Research Program, the RGK Foundation, the Gilder Foundation and the Betty Anne Asche Murray Distinguished Professorship. STR DNA fingerprinting was done by the Cancer Center Support Grant-funded Characterized Cell Line core, NCI CA016672. We thank D. Ruder, D. Reynolds, J. Seymour, Drs T. Miyake, T. Hisamatsu, R. Langley and the members of the histology and flow cytometry facilities at the University of Texas M.D. Anderson Cancer Center for technical assistance.

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms11169

Cite this

Wu, S. Y., Rupaimoole, R., Shen, F., Pradeep, S., Pecot, C. V., Ivan, C., Nagaraja, A. S., Gharpure, K. M., Pham, E., Hatakeyama, H., McGuire, M. H., Haemmerle, M., Vidal-Anaya, V., Olsen, C., Rodriguez-Aguayo, C., Filant, J., Ehsanipour, E. A., Herbrich, S. M., Maiti, S. N., ... Sood, A. K. (2016). A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer. Nature communications, 7, Article 11169. https://doi.org/10.1038/ncomms11169

Wu, SY, Rupaimoole, R, Shen, F, Pradeep, S, Pecot, CV, Ivan, C, Nagaraja, AS, Gharpure, KM, Pham, E, Hatakeyama, H, McGuire, MH, Haemmerle, M, Vidal-Anaya, V, Olsen, C, Rodriguez-Aguayo, C, Filant, J, Ehsanipour, EA, Herbrich, SM, Maiti, SN, Huang, L, Kim, JH, Zhang, X, Han, HD, Armaiz-Pena, GN, Seviour, EG, Tucker, S, Zhang, M, Yang, D, Cooper, LJN, Ali-Fehmi, R, Bar-Eli, M, Lee, JS, Ram, PT, Baggerly, KA, Lopez-Berestein, G, Hung, MC & Sood, AK 2016, 'A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer', Nature communications, vol. 7, 11169. https://doi.org/10.1038/ncomms11169

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title = "A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer",

abstract = "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.",

author = "Wu, {Sherry Y.} and Rajesha Rupaimoole and Fangrong Shen and Sunila Pradeep and Pecot, {Chad V.} and Cristina Ivan and Nagaraja, {Archana S.} and Gharpure, {Kshipra M.} and Elizabeth Pham and Hiroto Hatakeyama and McGuire, {Michael H.} and Monika Haemmerle and Viviana Vidal-Anaya and Courtney Olsen and Cristian Rodriguez-Aguayo and Justyna Filant and Ehsanipour, {Ehsan A.} and Herbrich, {Shelley M.} and Maiti, {Sourindra N.} and Li Huang and Kim, {Ji Hoon} and Xinna Zhang and Han, {Hee Dong} and Armaiz-Pena, {Guillermo N.} and Seviour, {Elena G.} and Sue Tucker and Min Zhang and Da Yang and Cooper, {Laurence J.N.} and Rouba Ali-Fehmi and Menashe Bar-Eli and Lee, {Ju Seog} and Ram, {Prahlad T.} and Baggerly, {Keith A.} and Gabriel Lopez-Berestein and Hung, {Mien Chie} and Sood, {Anil K.}",

note = "Funding Information: S.Y.W. is supported by the Ovarian Cancer Research Fund Alliance, Foundation for Womens Cancer, Texas Center for Cancer Nanomedicine and the Cancer Prevention Research Institute of Texas training grants (RP101502 and RP101489). R.R. is supported by the Russell and Diana Hawkins Family Foundation Discovery Fellowship. F.S. is supported by the Jiangsu Health International Exchange Program Fellowship. S.P. and G.N.A.-P. are supported by the Foundation for Womens Cancer. C.V.P. was supported by the NCI T32 training grant CA009666. E.P. is supported by a postdoctoral fellowship from the Canadian Institutes of Health Research and a Trainee Travel Award from Ovarian Cancer Canada. M.H. is supported by the Deutsche Forschungsgemeinschaft Research Fellowship. L.J.N.C. has ownership interests at Intrexon, Targazyme and Ziopharm; has patents with Sangamo BioSciences, reports receiving speakers bureau honoraria from Miltenyi; is a consultant/advisory board member for Ferring Pharmaceuticals and GE Healthcare; and reports receiving commercial research grants from Immatics US. Portions of this work were supported by the NIH (GM100777-01, GM086937-01, GM084552-04, CA016672, CA109298, P50 CA083639, P50 CA098258, CA128797, U54 CA151668, UH2 TR000943, U24CA143835 and P30CA16672), NCI-DHHS-NIH T32 Training grant (T32 CA101642), the DOD (OC120547 and OC093416), the Ovarian Cancer Research Fund, Inc. (Program Project Development Grant), the Blanton-Davis Ovarian Cancer Research Program, the RGK Foundation, the Gilder Foundation and the Betty Anne Asche Murray Distinguished Professorship. STR DNA fingerprinting was done by the Cancer Center Support Grant-funded Characterized Cell Line core, NCI CA016672. We thank D. Ruder, D. Reynolds, J. Seymour, Drs T. Miyake, T. Hisamatsu, R. Langley and the members of the histology and flow cytometry facilities at the University of Texas M.D. Anderson Cancer Center for technical assistance.",

year = "2016",

month = apr,

day = "4",

doi = "10.1038/ncomms11169",

language = "English",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

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TY - JOUR

T1 - A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer

AU - Wu, Sherry Y.

AU - Rupaimoole, Rajesha

AU - Shen, Fangrong

AU - Pradeep, Sunila

AU - Pecot, Chad V.

AU - Ivan, Cristina

AU - Nagaraja, Archana S.

AU - Gharpure, Kshipra M.

AU - Pham, Elizabeth

AU - Hatakeyama, Hiroto

AU - McGuire, Michael H.

AU - Haemmerle, Monika

AU - Vidal-Anaya, Viviana

AU - Olsen, Courtney

AU - Rodriguez-Aguayo, Cristian

AU - Filant, Justyna

AU - Ehsanipour, Ehsan A.

AU - Herbrich, Shelley M.

AU - Maiti, Sourindra N.

AU - Huang, Li

AU - Kim, Ji Hoon

AU - Zhang, Xinna

AU - Han, Hee Dong

AU - Armaiz-Pena, Guillermo N.

AU - Seviour, Elena G.

AU - Tucker, Sue

AU - Zhang, Min

AU - Yang, Da

AU - Cooper, Laurence J.N.

AU - Ali-Fehmi, Rouba

AU - Bar-Eli, Menashe

AU - Lee, Ju Seog

AU - Ram, Prahlad T.

AU - Baggerly, Keith A.

AU - Lopez-Berestein, Gabriel

AU - Hung, Mien Chie

AU - Sood, Anil K.

N1 - Funding Information: S.Y.W. is supported by the Ovarian Cancer Research Fund Alliance, Foundation for Womens Cancer, Texas Center for Cancer Nanomedicine and the Cancer Prevention Research Institute of Texas training grants (RP101502 and RP101489). R.R. is supported by the Russell and Diana Hawkins Family Foundation Discovery Fellowship. F.S. is supported by the Jiangsu Health International Exchange Program Fellowship. S.P. and G.N.A.-P. are supported by the Foundation for Womens Cancer. C.V.P. was supported by the NCI T32 training grant CA009666. E.P. is supported by a postdoctoral fellowship from the Canadian Institutes of Health Research and a Trainee Travel Award from Ovarian Cancer Canada. M.H. is supported by the Deutsche Forschungsgemeinschaft Research Fellowship. L.J.N.C. has ownership interests at Intrexon, Targazyme and Ziopharm; has patents with Sangamo BioSciences, reports receiving speakers bureau honoraria from Miltenyi; is a consultant/advisory board member for Ferring Pharmaceuticals and GE Healthcare; and reports receiving commercial research grants from Immatics US. Portions of this work were supported by the NIH (GM100777-01, GM086937-01, GM084552-04, CA016672, CA109298, P50 CA083639, P50 CA098258, CA128797, U54 CA151668, UH2 TR000943, U24CA143835 and P30CA16672), NCI-DHHS-NIH T32 Training grant (T32 CA101642), the DOD (OC120547 and OC093416), the Ovarian Cancer Research Fund, Inc. (Program Project Development Grant), the Blanton-Davis Ovarian Cancer Research Program, the RGK Foundation, the Gilder Foundation and the Betty Anne Asche Murray Distinguished Professorship. STR DNA fingerprinting was done by the Cancer Center Support Grant-funded Characterized Cell Line core, NCI CA016672. We thank D. Ruder, D. Reynolds, J. Seymour, Drs T. Miyake, T. Hisamatsu, R. Langley and the members of the histology and flow cytometry facilities at the University of Texas M.D. Anderson Cancer Center for technical assistance.

PY - 2016/4/4

Y1 - 2016/4/4

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms11169

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SN - 2041-1723

VL - 7

JO - Nature communications

JF - Nature communications

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ER -

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

Abstract

Bibliographical note

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UN SDGs

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