OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers

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dc.citation.articleNumber13106en_US
dc.citation.journalTitleScientific Reportsen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorMonroig-Bosque, Paloma del C.en_US
dc.contributor.authorShah, Maitri Y.en_US
dc.contributor.authorFu, Xiaoen_US
dc.contributor.authorFuentes-Mattei, Enriqueen_US
dc.contributor.authorLing, Huien_US
dc.contributor.authorIvan, Cristinaen_US
dc.contributor.authorNouraee, Nazilaen_US
dc.contributor.authorHuang, Beibeien_US
dc.contributor.authorChen, Luen_US
dc.contributor.authorPileczki, Valentinaen_US
dc.contributor.authorRedis, Roxana S.en_US
dc.contributor.authorJung, Eun-Jungen_US
dc.contributor.authorZhang, Xinen_US
dc.contributor.authorLehrer, Michaelen_US
dc.contributor.authorNagvekar, Rahulen_US
dc.contributor.authorMafra, Ana Carolina P.en_US
dc.contributor.authorMonroig-Bosque, Maria del Maren_US
dc.contributor.authorIrimie, Alexandraen_US
dc.contributor.authorRivera, Carlosen_US
dc.contributor.authorDumitru, Calin Danen_US
dc.contributor.authorBerindan-Neagoe, Ioanaen_US
dc.contributor.authorNikonowicz, Edward P.en_US
dc.contributor.authorZhang, Shuxingen_US
dc.contributor.authorCalin, George A.en_US
dc.date.accessioned2018-11-15T17:16:14Zen_US
dc.date.available2018-11-15T17:16:14Zen_US
dc.date.issued2018en_US
dc.description.abstractThe pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies. In this study, we devised a strategy to screen for small molecule inhibitors that specifically inhibit, directly or indirectly, miR-10b (SMIRs) which is overexpressed in metastatic tumors. We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo. In addition, we showed that the efficacy of linifanib to inhibit tyrosine kinases was reduced by high miR-10b levels. When the level of miR-10b is high, it can "hijack" the linifanib and reduce its kinase inhibitory effects in cancer resulting in reduced anti-tumor efficacy. In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described "hijacking" effect, may be used as a biomarker to select patients for linifanib treatment.en_US
dc.identifier.citationMonroig-Bosque, Paloma del C., Shah, Maitri Y., Fu, Xiao, et al.. "OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers." <i>Scientific Reports,</i> 8, (2018) Springer Nature: https://doi.org/10.1038/s41598-018-30989-3.en_US
dc.identifier.digitals41598-018-30989-3en_US
dc.identifier.doihttps://doi.org/10.1038/s41598-018-30989-3en_US
dc.identifier.urihttps://hdl.handle.net/1911/103345en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleOncomiR-10b hijacks the small molecule inhibitor linifanib in human cancersen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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