Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

Xiuhui Chen, Lingegowda S. Mangala, Linda Mooberry, Emine Bayraktar, Santosh K. Dasari, Shaolin Ma, Cristina Ivan, Karem A. Court, Cristian Rodriguez-Aguayo, Recep Bayraktar, Sangram Raut, Nirupama Sabnis, Xianchao Kong, Xianbin Yang, Gabriel Lopez-Berestein, Andras G. Lacko, Anil K. Sood

Research output: Contribution to journalArticle

Abstract

Current anti-angiogenic therapy for cancer is based mainly on inhibition of the vascular endothelial growth factor pathway. However, due to the transient and only modest benefit from such therapy, additional approaches are needed. Deregulation of microRNAs (miRNAs) has been demonstrated to be involved in tumor angiogenesis and offers opportunities for a new therapeutic approach. However, effective miRNA-delivery systems are needed for such approaches to be successful. In this study, miRNA profiling of patient data sets, along with in vitro and in vivo experiments, revealed that miR-204-5p could promote angiogenesis in ovarian tumors through THBS1. By binding with scavenger receptor class B type 1 (SCARB1), reconstituted high-density lipoprotein–nanoparticles (rHDL–NPs) were effective in delivering miR-204-5p inhibitor (miR-204-5p-inh) to tumor sites to suppress tumor growth. These results offer a new understanding of miR-204-5p in regulating tumor angiogenesis.

Original languageEnglish
Pages (from-to)6095-6108
Number of pages14
JournalOncogene
Volume38
Issue number33
DOIs
StatePublished - 15 Aug 2019

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MicroRNAs
Ovarian Neoplasms
Neoplasms
CD36 Antigens
Vascular Endothelial Growth Factor A
Therapeutics
Growth

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Chen, X., Mangala, L. S., Mooberry, L., Bayraktar, E., Dasari, S. K., Ma, S., ... Sood, A. K. (2019). Identifying and targeting angiogenesis-related microRNAs in ovarian cancer. Oncogene, 38(33), 6095-6108. https://doi.org/10.1038/s41388-019-0862-y
Chen, Xiuhui ; Mangala, Lingegowda S. ; Mooberry, Linda ; Bayraktar, Emine ; Dasari, Santosh K. ; Ma, Shaolin ; Ivan, Cristina ; Court, Karem A. ; Rodriguez-Aguayo, Cristian ; Bayraktar, Recep ; Raut, Sangram ; Sabnis, Nirupama ; Kong, Xianchao ; Yang, Xianbin ; Lopez-Berestein, Gabriel ; Lacko, Andras G. ; Sood, Anil K. / Identifying and targeting angiogenesis-related microRNAs in ovarian cancer. In: Oncogene. 2019 ; Vol. 38, No. 33. pp. 6095-6108.
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Chen, X, Mangala, LS, Mooberry, L, Bayraktar, E, Dasari, SK, Ma, S, Ivan, C, Court, KA, Rodriguez-Aguayo, C, Bayraktar, R, Raut, S, Sabnis, N, Kong, X, Yang, X, Lopez-Berestein, G, Lacko, AG & Sood, AK 2019, 'Identifying and targeting angiogenesis-related microRNAs in ovarian cancer', Oncogene, vol. 38, no. 33, pp. 6095-6108. https://doi.org/10.1038/s41388-019-0862-y

Identifying and targeting angiogenesis-related microRNAs in ovarian cancer. / Chen, Xiuhui; Mangala, Lingegowda S.; Mooberry, Linda; Bayraktar, Emine; Dasari, Santosh K.; Ma, Shaolin; Ivan, Cristina; Court, Karem A.; Rodriguez-Aguayo, Cristian; Bayraktar, Recep; Raut, Sangram; Sabnis, Nirupama; Kong, Xianchao; Yang, Xianbin; Lopez-Berestein, Gabriel; Lacko, Andras G.; Sood, Anil K.

In: Oncogene, Vol. 38, No. 33, 15.08.2019, p. 6095-6108.

Research output: Contribution to journalArticle

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AU - Mangala, Lingegowda S.

AU - Mooberry, Linda

AU - Bayraktar, Emine

AU - Dasari, Santosh K.

AU - Ma, Shaolin

AU - Ivan, Cristina

AU - Court, Karem A.

AU - Rodriguez-Aguayo, Cristian

AU - Bayraktar, Recep

AU - Raut, Sangram

AU - Sabnis, Nirupama

AU - Kong, Xianchao

AU - Yang, Xianbin

AU - Lopez-Berestein, Gabriel

AU - Lacko, Andras G.

AU - Sood, Anil K.

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AB - Current anti-angiogenic therapy for cancer is based mainly on inhibition of the vascular endothelial growth factor pathway. However, due to the transient and only modest benefit from such therapy, additional approaches are needed. Deregulation of microRNAs (miRNAs) has been demonstrated to be involved in tumor angiogenesis and offers opportunities for a new therapeutic approach. However, effective miRNA-delivery systems are needed for such approaches to be successful. In this study, miRNA profiling of patient data sets, along with in vitro and in vivo experiments, revealed that miR-204-5p could promote angiogenesis in ovarian tumors through THBS1. By binding with scavenger receptor class B type 1 (SCARB1), reconstituted high-density lipoprotein–nanoparticles (rHDL–NPs) were effective in delivering miR-204-5p inhibitor (miR-204-5p-inh) to tumor sites to suppress tumor growth. These results offer a new understanding of miR-204-5p in regulating tumor angiogenesis.

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Chen X, Mangala LS, Mooberry L, Bayraktar E, Dasari SK, Ma S et al. Identifying and targeting angiogenesis-related microRNAs in ovarian cancer. Oncogene. 2019 Aug 15;38(33):6095-6108. https://doi.org/10.1038/s41388-019-0862-y