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

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dc.citation.articleNumber13106
dc.citation.journalTitleScientific Reports
dc.citation.volumeNumber8
dc.contributor.authorMonroig-Bosque, Paloma del C.
dc.contributor.authorShah, Maitri Y.
dc.contributor.authorFu, Xiao
dc.contributor.authorFuentes-Mattei, Enrique
dc.contributor.authorLing, Hui
dc.contributor.authorIvan, Cristina
dc.contributor.authorNouraee, Nazila
dc.contributor.authorHuang, Beibei
dc.contributor.authorChen, Lu
dc.contributor.authorPileczki, Valentina
dc.contributor.authorRedis, Roxana S.
dc.contributor.authorJung, Eun-Jung
dc.contributor.authorZhang, Xin
dc.contributor.authorLehrer, Michael
dc.contributor.authorNagvekar, Rahul
dc.contributor.authorMafra, Ana Carolina P.
dc.contributor.authorMonroig-Bosque, Maria del Mar
dc.contributor.authorIrimie, Alexandra
dc.contributor.authorRivera, Carlos
dc.contributor.authorDumitru, Calin Dan
dc.contributor.authorBerindan-Neagoe, Ioana
dc.contributor.authorNikonowicz, Edward P.
dc.contributor.authorZhang, Shuxing
dc.contributor.authorCalin, George A.
dc.date.accessioned2018-11-15T17:16:14Z
dc.date.available2018-11-15T17:16:14Z
dc.date.issued2018
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.
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.
dc.identifier.digitals41598-018-30989-3
dc.identifier.doihttps://doi.org/10.1038/s41598-018-30989-3
dc.identifier.urihttps://hdl.handle.net/1911/103345
dc.language.isoeng
dc.publisherSpringer Nature
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleOncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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