MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma
dc.contributor.author | Moody, Hannah L. | |
dc.contributor.author | Lind, M. | |
dc.contributor.author | Maher, S.G. | |
dc.date.accessioned | 2020-09-27T09:06:48Z | |
dc.date.available | 2020-09-27T09:06:48Z | |
dc.date.issued | 2017-09-15 | |
dc.identifier.citation | Moody 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.uri | http://hdl.handle.net/10454/18034 | |
dc.description | Yes | en_US |
dc.description.abstract | Malignant 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.iso | en | en_US |
dc.relation.isreferencedby | https://doi.org/10.1016/j.omtn.2017.07.001 | en_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.subject | Malignant pleural mesothelioma | en_US |
dc.subject | microRNA-31 | en_US |
dc.subject | Chemoresistance | en_US |
dc.subject | Cisplatin | en_US |
dc.subject | ABCB9 | en_US |
dc.title | MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma | en_US |
dc.status.refereed | Yes | en_US |
dc.date.Accepted | 2017-09-08 | |
dc.type | Article | en_US |
dc.type.version | Published version | en_US |
refterms.dateFOA | 2020-09-27T09:07:05Z |