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dc.contributor.authorMoody, Hannah L.
dc.contributor.authorLind, M.
dc.contributor.authorMaher, S.G.
dc.date.accessioned2020-09-27T09:06:48Z
dc.date.available2020-09-27T09:06:48Z
dc.date.issued2017-09-15
dc.identifier.citationMoody HL, Lind M and Maher SG (2017) MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma. Molecular Therapy: Nucleic Acids. 8: 317-329.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18034
dc.descriptionYesen_US
dc.description.abstractMalignant pleural mesothelioma (MPM) is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31) is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin. Although miR-31 re-expression increased chemoresistance, paradoxically, a higher relative intracellular accumulation of platinum was detected. This was coupled to a significantly decreased intranuclear concentration of platinum. Linked with a downregulation of OCT1, a bipotential transcriptional regulator with multiple miR-31 target binding sites, we subsequently identified an indirect miR-31-mediated upregulation of ABCB9, a transporter associated with drug accumulation in lysosomes, and increased uptake of platinum to lysosomes. However, when overexpressed directly, ABCB9 promoted cellular chemosensitivity, suggesting that miR-31 promotes chemoresistance largely via an ABCB9-independent mechanism. Overall, our data suggest that miR-31 loss from MPM tumors promotes chemosensitivity and may be prognostically beneficial in the context of therapeutic sensitivity.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.omtn.2017.07.001en_US
dc.rights(c) 2017 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/)en_US
dc.subjectMalignant pleural mesotheliomaen_US
dc.subjectmicroRNA-31en_US
dc.subjectChemoresistanceen_US
dc.subjectCisplatinen_US
dc.subjectABCB9en_US
dc.titleMicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesotheliomaen_US
dc.status.refereedYesen_US
dc.date.Accepted2017-09-08
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2020-09-27T09:07:05Z


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